Biology subjects

Carrington, M.

Publications and source records attributed to Carrington, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Self-reactive human CD8⁺ T cells restricted by HLA-E mediate immunoregulatory and antiviral functions

HLA-E constitutively presents self VL9 peptides on healthy cells, signaling an intact HLA class I pathway and protecting cells from natural killer cell attack. Beyond this canonical role, HLA-E-restricted CD8 T cells that recognize foreign pathogen peptides have emerged as mediators of immunity in multiple human infections, with orthologous responses conferring unprecedented protection in an HIV vaccine model. However, the poor stability of most pathogen-derived HLA-E ligands raises the possibility that additional modes of HLA-E-restricted recognition remain undiscovered. Here, we establish an alternative paradigm in which HLA-E-restricted CD8+ T cells recognize disease-associated increases in self-VL9/HLA-E rather than foreign antigen. These cells, which we term E-sensors, integrate activating and inhibitory signals to discriminate physiological from pathological levels of HLA-E expression. We demonstrate that E-sensors selectively eliminate highly activated, proliferating immune cells that express high levels of HLA-E, establishing a mechanistically resolved pathway of human CD8+ T cell immunoregulation. E-sensors also recognize pathogen-induced HLA-E upregulation and directly eliminate infected cells without prior pathogen-specific priming, demonstrating immediate immunosurveillance through recognition of increased self. Consistent with this antiviral function, we establish E-sensors as a previously unrecognized component of spontaneous HIV immune control in persons who naturally control infection. Together, our findings establish a pathway of human immunosurveillance and immunoregulation in which CD8 T cells detect pathological increases in a constitutively expressed non-classical HLA class I molecule presenting a conserved self-peptide. This disease-agnostic mechanism of immune recognition has implications across infection, cancer, autoimmune disease, and other pathologies that upregulate HLA-E. Unlike classical HLA class I molecules, the near-monomorphic nature of HLA-E further positions this pathway as an untapped effector axis, warranting investigation as a potential target for immune interventions.

immunology↗

bioRxiv2026

An African trypanosome surface protein inhibits amplification of the complement system

African trypanosomes replicate within the blood and tissue spaces of their mammalian hosts. As extracellular pathogens, they are constantly exposed to immune cells and molecules and are susceptible to killing by components of the complement system. In this study, we conducted a large-scale screen of a panel of human complement components against a set of putative T. brucei surface proteins and discovered a novel T. brucei receptor that binds to complement Factor B. Biochemical and structural characterisation of this protein revealed it to be a potent inhibitor of the C3bBb convertase, a central enzyme in amplification of the complement cascade. Structural studies show that this C3bBb receptor bridges C3b and Bb in a conformation which is incompatible with its catalytic activity, directly blocking C3bBb convertase function. This reveals a novel mechanism of C3bBb convertase regulation and deepens insight into how the African trypanosome cell surface has evolved to evade complement-mediated killing.

immunology↗

bioRxiv2026

A Trypanosoma brucei gambiense gene variant confers human serum resistance

Most species of African trypanosomes cannot infect humans due to the presence in our blood of trypanolytic factors (TLFs). These lipoprotein particles contain the apolipoprotein L1 (ApoLI) toxin which, when internalised by trypanosomes, forms pores and causes cell death. However, two subspecies of Trypanosoma brucei have evolved resistance to TLFs and cause Human African Trypanosomiasis (HAT). The mechanism of resistance of T. b. rhodesiense requires a single additional molecule, the serum resistance associated protein SRA. However, the mechanism of resistance of T. b. gambiense, which causes HAT in West Africa, has not been fully understood. Here we identify a single polymorphic variant of a PLAC8-domain containing protein which is required for human serum resistance and call this T. b. gambiense-specific resistance variant, TgsRV. African trypanosomes are coated with a dense layer of many copies of one member of the variant surface glycoprotein protein family (VSGs). For cells expressing some VSGs, TgsRV is sufficient for human serum resistance, while cells which express other VSGs require a second protein, TgsGP in addition to TgsRV. We therefore complete the identification of the molecular players required for human serum resistance by the African trypanosomes.

microbiology↗

bioRxiv2025

An auxin-inducible degron system for trypanosomes

The ability to specifically degrade one protein in a cell provides an immediate insight into any resulting phenotype and thus function that may be occluded by secondary effects using other techniques. The auxin inducible degron is a method developed to achieve this end and is effective in mammalian and yeast cells. The approach is dependent on the recognition of a tagged target protein by an endogenous E3 ubiquitin ligase modified by the expression of a plant F-box protein. This approach was initially unsuccessful in trypanosomes probably due to a lack of interaction between the endogenous E3 ubiquitin ligase and the plant F-box protein. This was overcome by expressing the entire rice E3 ubiquitin ligase in trypanosomes and here we describe the production of the auxin inducible degron competent cell lines and tagging of target genes.

molecular biology↗

bioRxiv2025

Insights from aquaporin structures into drug-resistant sleeping sickness

Trypanosoma brucei is the causal agent of African trypanosomiasis in humans and animals, the latter resulting in significant negative economic impacts in afflicted areas of the world. Resistance has arisen to the trypanocidal drugs pentamidine and melarsoprol through mutations in the aquaglyceroporin TbAQP2 that prevent their uptake. Here we use cryogenic electron microscopy to determine the structure of TbAQP2 from Trypanosoma brucei, bound to either the substrate glycerol or to the sleeping sickness drugs, pentamidine or melarsoprol. The drugs bind within the AQP2 channel at a site completely overlapping that of glycerol. Mutations leading to a drug-resistant phenotype were found in the channel lining. Molecular dynamics simulations showed the channel can be traversed by pentamidine, with a low energy binding site at the centre of the channel, flanked by regions of high energy association at the extracellular and intracellular ends. Drug-resistant TbAQP2 mutants are still predicted to bind pentamidine, but the much weaker binding in the centre of the channel observed in the MD simulations would be insufficient to compensate for the high energy processes of ingress and egress, hence impairing transport at pharmacologically relevant concentrations. The structures of drug-bound TbAQP2 represent a novel paradigm for drug-transporter interactions that could provide new mechanisms for targeting drugs into pathogens and human cells.

molecular biology↗

bioRxiv2025

Cell surface localisation of GPI-anchored receptors in Trypanosoma brucei

Trypanosoma brucei, the causal agent of Human and Animal African trypanosomiasis proliferates in the extracellular milieu of mammals. It acquires host macromolecular nutrients, by receptor mediated endocytosis. The best characterised cell surface receptor is for transferrin (TfR) and it has been reported to be preferentially localised in the flagellar pocket domain of the plasma membrane, the sole site of endocytosis. In this location the TfR may be inaccessible to adaptive immune system effectors. The T. brucei genome encodes [~]15 TfR variants, and here we compared two, the first attached to the plasma membrane by a single glycosylphosphatidylinositol (GPI)-anchor and the other by two. Transferrin uptake kinetics were similar and rapid for both. Unexpectedly, initial binding of transferrin occurred over the whole cell surface suggesting the TfR was not localised solely in the flagellar pocket. This localisation was confirmed by immunofluorescence assays and was independent of the number of GPI-anchors. Two other GPI-anchored receptors were investigated to determine whether localisation to the whole cell surface was a general property of GPI-anchored receptors. Haptoglobin-haemoglobin uptake assays and immunofluorescence localisation of complement factor H receptor showed both were also whole cell surface localised. The mechanisms by which trypanosome receptors are protected from antibody-mediated attack are more complex than hiding in a pocket.

microbiology↗

bioRxiv2024

Acute infectious mononucleosis generates persistent, functional EBNA-1 antibodies with high cross-reactivity to alpha crystalline beta

Epstein-Barr Virus (EBV) infects over 95% of the worlds population and is the most common cause of infectious mononucleosis (IM). Epidemiologic studies have linked EBV with certain cancers or autoimmune conditions, including multiple sclerosis (MS). Recent studies suggest that molecular mimicry between EBV proteins, particularly EBV nuclear antigen 1 (EBNA-1), and self-proteins is a plausible mechanism through which EBV infection may contribute to the development of autoimmune disorders. We used a systems immunology approach to investigate the magnitude, specificity, and functional properties of EBNA-1 specific antibodies in a cohort of 97 young adults with IM from presentation through 1-year post-primary infection compared to a control cohort of EBV-seropositive individuals. Levels of EBNA-1 specific IgG1 and IgG3 binding antibodies increased over the course of infection. EBNA-1 antibodies capable of mediating antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent complement deposition (ADCD) were detected at or after 6 months. Binding and ADCP- and ADCD-leveraged antibodies primarily targeted a region of EBNA-1 known to elicit cross-reactive antibodies to several self-peptides in individuals with MS. Significantly higher binding and ADCD-active antibodies targeting EBNA-1 were observed in individuals with at least one HLA-DRB1*15:01 allele, a known genetic risk factor for MS; Importantly, high levels of antibodies capable of binding alpha crystalline beta (CRYAB) and mediating complement deposition were detected at 6 months and 1-year following IM; CRYAB antibodies were resistant to denaturing forces, indicating an affinity matured response. Blocking experiments confirmed that CRYAB antibodies were cross-reactive with EBNA-1. Altogether, these results demonstrate that high levels of functional antibodies targeting EBNA-1 are generated in early EBV infection, some of which are cross-reactive with CRYAB. Further investigation is warranted to determine how these antibody responses may contribute to the subsequent development of MS.

immunology↗

bioRxiv2024

Immunopeptidomics informs discovery and delivery of Mycobacterium tuberculosis MHC-II antigens for vaccine design

No currently licensed vaccine reliably prevents pulmonary tuberculosis (TB), a leading cause of infectious disease mortality. Developing effective new vaccines will require identifying which of the roughly 4000 proteins in the Mycobacterium tuberculosis (Mtb) proteome are presented on MHC class II (MHC-II) by infected human phagocytes and can be recognized by CD4+ T cells to mediate protective immunity. Vaccines must also elicit T cell responses recognizing the same peptide-MHC complexes presented by infected cells, and successful presentation of target human MHC-II peptides is currently challenging to evaluate and optimize. Here, we define antigenic targets for TB vaccine development by using mass spectrometry (MS) for proteome-wide discovery of Mtb epitopes presented on MHC-II by infected human cells. We next iteratively design and evaluate candidate mRNA vaccine immunogens, revealing design principles that enhance presentation of target MHC-II peptides. Our results will inform the development of new TB vaccine candidates.

microbiology↗

bioRxiv2024

PathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification

Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobials-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropriate targets for T cell priming vaccines remains challenging. Mass spectrometry (MS) analysis of peptides presented on major histocompatibility complexes (MHCs) can identify potential targets for protective T cell responses in a proteome-wide manner. However, pathogen-derived peptides are outnumbered by self peptides in the MHC repertoire and may be missed in untargeted MS analyses. Here we present a novel approach, termed PathMHC, that uses computational analysis of untargeted MS data followed by targeted MS to discover novel pathogen-derived MHC peptides more efficiently than untargeted methods alone. We applied this workflow to identify MHC peptides derived from multiple microbes, including potential vaccine targets presented on MHC-I by human dendritic cells infected with Mycobacterium tuberculosis. PathMHC will facilitate antigen discovery campaigns for vaccine development.

microbiology↗

bioRxiv2024

Intron-loss in Kinetoplastea correlates with a non-functional EJC and loss of NMD factors

In metazoans, mRNA quality is tightly monitored from transcription to translation. A key role lies with the exon junction complex (EJC) that is placed upstream of the exon-exon junction after splicing. The EJC inner core is composed of Magoh, Y14, eIF4AIII and BTZ and the outer core of proteins involved in mRNA splicing (CWC22), export (Yra1), translation (PYM) and non-sense mediated decay (NMD, UPF1/2/3). The protozoan parasite Trypanosoma brucei encodes only two genes with introns, but all mRNAs are processed by trans-splicing. The presence of the three core EJC proteins and a potential BTZ homologue (Rbp25) in trypanosomes has been suggested as an adaptation of the EJC function to mark trans-spliced mRNAs. We analysed trypanosome EJC components and noticed major differences between eIF4AIII and Magoh/Y14: (i) whilst eIF4AIII is essential, knocking out both Magoh and Y14 elicits only a mild growth phenotype and does not affect processing, export or stability of the two cis-spliced mRNAs (ii) eIF4AIII localization is mostly nucleolar, with a minor proportion in the nucleoplasm and cytoplasm, while Magoh and Y14 are nucleolar and nucleoplasmic but excluded from the cytoplasm (iii) eIF4AIII associates with nucleolar proteins (including NOM1/Sgd1p) and the splicing factor CWC22, but not with Y14 or Magoh, while Magoh and Y14 associate with each other, but not with eIF4AIII, CWC22 or the nucleolar proteins. Our data argue against the presence of a functional EJC in trypanosomes, but rather indicate that eIF4AIII adopted non-EJC related, essential functions, while Magoh and Y14 became redundant. Trypanosomes also possess homologues to the NMD proteins UPF1 and UPF2. We found that depletion of UPF1 causes only a minor reduction in growth and detailed phylogenetic analyses show several independent losses of UPF1 and UPF2, as well as total loss of UPF3 in the Kinetoplastida group. The data indicate that UPF1-dependent NMD is not essential in trypanosomes consistent with the observation that the cells tolerate the presence of mRNAs with allele-specific, endogenous PTCs (premature termination codons). Altogether, our comprehensive analyses of conserved components provide no evidence for a canonical EJC or NMD pathway in (almost) intron-less trypanosomatids.

biochemistry↗

bioRxiv2023

Understanding the heterogeneity of alloreactive natural killer cell function inkidney transplantation

Human Natural Killer (NK) cells are heterogeneous lymphocytes regulated by variegated arrays of germline-encoded activating and inhibitory receptors. They acquire the ability to detect polymorphic self-antigen via NKG2A/HLA-E or KIR/HLA-I ligand interactions through an education process. Correlations among HLA/KIR genes, kidney transplantation pathology and outcomes suggest that NK cells participate in allograft injury, but mechanisms linking NK HLA/KIR education to antibody-independent pathological functions remain unclear. We used CyTOF to characterize pre- and post-transplant peripheral blood NK cell phenotypes/functions before and after stimulation with allogeneic donor cells. Unsupervised clustering identified unique NK cell subpopulations present in varying proportions across patients, each of which responded heterogeneously to donor cells based on donor ligand expression patterns. Analyses of pre-transplant blood showed that educated, NKG2A/KIR-expressing NK cells responded greater than non-educated subsets to donor stimulators, and this heightened alloreactivity persisted > 6 months post-transplant despite immunosuppression. In distinct test and validation sets of patients participating in two clinical trials, pre-transplant donor-induced release of NK cell Ksp37, a cytotoxicity mediator, correlated with 2-year and 5-year eGFR. The findings explain previously reported associations between NK cell genotypes and transplant outcomes and suggest that pre-transplant NK cell analysis could function as a risk-assessment biomarker for transplant outcomes.

immunology↗

bioRxiv2023

Molecular mechanism of complement inhibition by the trypanosome receptor ISG65

African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but becomes covalently deposited onto the surfaces of pathogens after proteolytic cleavage to C3b. Membrane-associated C3b triggers different complement-mediated effectors which promote pathogen clearance. To counter complement-mediated clearance, African trypanosomes have a cell surface receptor, ISG65, which binds to C3b and which decreases the rate of trypanosome clearance in an infection model. However, the mechanism by which ISG65 reduces C3b function has not been determined. We reveal through cryogenic electron microscopy that ISG65 has two distinct binding sites for C3b, only one of which is available in C3 and C3d. We show that ISG65 does not block the formation of C3b or the function of the C3 convertase which catalyses the surface deposition of C3b. However, we show that ISG65 forms a specific conjugate with C3b, perhaps acting as a decoy. ISG65 also occludes the binding sites for complement receptors 2 and 3, which may disrupt recruitment of immune cells, including B cells, phagocytes and granulocytes. This suggests that ISG65 protects trypanosomes by combining multiple approaches to dampen the complement cascade. Impact StatementA structure derived from cryogenic electron microscopy shows how ISG65, an African trypanosome receptor that aids virulence, binds C3b and suggests mechanisms through which ISG65 might aid complement resistance.

microbiology↗

bioRxiv2022

A common neural code for representing imagined and inferred tastes

Inferences about the taste of foods are a key aspect of our everyday experience of food choice. Despite this, gustatory mental imagery is a relatively under-studied aspect of our mental lives. In the present study, we examined subjects during high-field fMRI as they actively imagined basic tastes and subsequently viewed pictures of foods dominant in those specific taste qualities. Imagined tastes elicited activity in the bilateral dorsal mid-insula, one of the primary cortical regions responsive to the experience of taste. In addition, within this region we reliably decoded imagined tastes according to their dominant quality - sweet, sour, or salty - thus indicating that, like actual taste, imagined taste activates distinct quality-specific neural patterns. Using a cross-task decoding analysis, we found that the neural patterns for imagined tastes and food pictures in the mid-insula were reliably similar and quality-specific, suggesting a common code for representing taste quality regardless of whether explicitly imagined or automatically inferred when viewing food. These findings have important implications for our understanding of the mechanisms of mental imagery and the multimodal nature of presumably primary sensory brain regions like the dorsal mid-insula.

neuroscience↗

bioRxiv2022

Genome-wide subcellular protein localisation in the flagellate parasite Trypanosoma brucei

Trypanosoma brucei is a prototypical trypanosomatid, an important group of human, animal and plant unicellular parasites. Understanding their complex cell architecture and life cycle is hindered since, as with most eukaryotic microbes, [~]50% of the proteins encoded in the genome have completely unknown function. Using fluorescence microscopy and cell lines expressing endogenously tagged proteins we mapped the subcellular localisation of 89% of the proteome, giving clues to function, defining the lineage-specific organelle adaptations for obligate parasitism and mapping the ultra-conserved cellular architecture of eukaryotes. This includes the single flagellum, vital for morphogenesis and pathology: the first comprehensive cartographic analysis of the flagellum in any organism. To demonstrate the power of this resource, we identify novel specialisation of organelle molecular composition through the cell cycle and in specialised subdomains. This is a transformative resource, important for hypothesis generation for both eukaryotic evolutionary molecular cell biology and fundamental parasite cell biology.

microbiology↗

bioRxiv2022

NKG2A and HLA-E define a novel alternative immune checkpoint axis in bladder cancer

PD-1/PD-L1-blockade immunotherapies have limited efficacy in the treatment of muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Here, we show that KLRC1 (NKG2A) expression associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in CD8Ahigh bladder tumors. The loss of antigen presentation is a common mechanism for tumor escape in bladder cancer. NKG2A+ CD8 T cells are able to circumvent HLA-ABC loss through TCR-independent cytotoxicity, which is partly mediated by DNAM-1. In bladder tumors, NKG2A is acquired on a subset of PD-1+ CD8 T cells, alongside stronger tissue-residency memory features, TCR-independent cytotoxicity and evidence of recent proliferation. HLA-E is low but variably expressed on bladder tumors. When expressed, NKG2A+ CD8 T cell anti-tumor responses to HLA-ABC-deficient tumors are inhibited and partly restored upon NKG2A blockade. Overall, our study identifies an alternative path for CD8 T cell exhaustion, that is mediated by NKG2A upregulation and TCR-independent cytotoxicity.

immunology↗

bioRxiv2021

Host Variation in Interferon, MHC Class I, Glycosylation, and Viral Transcription Genes Predict HIV Persistence

ObjectivePrior genomewide association studies have identified variation in MHC Class I alleles and CCR5{Delta}32 as genetic predictors of viral control, especially in "elite" controllers, individuals who remain virally suppressed in the absence of therapy. DesignCross-sectional genomewide association study. MethodsWe analyzed custom whole exome sequencing and direct HLA typing from 202 ART-suppressed HIV+ non-controllers in relation to four measures of the peripheral CD4+ T cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression. ResultsPreviously reported "protective" host genetic mutations related to viral setpoint (e.g., among elite controllers) were found to predict smaller HIV reservoir size. The HLA "protective" B*57:01 was associated with significantly lower HIV usRNA (q=3.3x10-3), and among the largest subgroup, European ancestry individuals, the CCR5{Delta}32 deletion was associated with smaller HIV tDNA (p=4.3x10-3) and usRNA (p=8.7x10-3). In addition, genomewide analysis identified several SNPs in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q=0.02), and the direction of these associations paralleled MX1 gene eQTL expression. ConclusionsWe observed a significant association between previously reported "protective" MHC class I alleles and CCR5{Delta}32 with the HIV reservoir size in non-controllers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.

genomics↗

bioRxiv2021

Black-necked spitting cobra (Naja nigricollis) phospholipases A2 cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket

African trypanosomes, such as Trypanosoma brucei, are flagellated protozoa which proliferate in mammals and cause a variety of diseases in people and animals. In a mammalian host, the external face of the African trypanosome plasma membrane is covered by a densely packed coat formed of variant surface glycoprotein (VSG), which counteracts the host adaptive immune response by antigenic variation. The VSG is attached to the external face of the plasma membrane by covalent attachment of the C-terminus to a glycosylphosphatidylinositol. As the trypanosome grows, newly synthesised VSG is added to the plasma membrane by vesicle fusion to the flagellar pocket, the sole location of exo- and endocytosis. Snake venoms contain dozens of components including proteases and phospholipases. Here, we investigated the effect of Naja nigricollis on T. brucei with the aim of describing the response of the trypanosome to hydrolytic attack on the VSG. We found no evidence for VGS hydrolysis however N. nigricollis venom caused: (i) an enlargement of the flagellar pocket, (ii) the Rab11 positive endosomal compartments to adopt an abnormal dispersed localisation, and (iii) a cell cycle arrest prior to cytokinesis. A single protein family, the phospholipases A2s present in N. nigricollis venom, was necessary and sufficient for the effects. This study provides new molecular insight into T. brucei biology and possibly describes mechanisms that could be exploited for T. brucei targeting.

microbiology↗

bioRxiv2021

Transmission of Candidatus Anaplasma camelii to laboratory animals by camel-specific keds, Hippobosca camelina

Anaplasmosis, caused by infection with bacteria of the genus Anaplasma is an important veterinary and zoonotic disease. The characterization of transmission has concentrated on ticks and little is known about non-tick vectors of livestock anaplasmosis. This study investigated the presence of Anaplasma spp. in camels in northern Kenya and whether the hematophagous camel ked, Hippobosca camelina, acts as a vector. Camels (n = 976) and > 10,000 keds were sampled over a three-year study period and the presence of Anaplasma species was determined by PCR-based assays targeting the Anaplasmataceae 16S rRNA gene. Camels were infected by Candidatus Anaplasma camelii occurring from 63 - 78% during the dry (September 2017), wet (June-July 2018), and late wet seasons (July-August 2019). 10 - 29% of camel keds harbored Ca. Anaplasma camelii acquired from infected camels during blood feeding. We determined whether Anaplasma positive camel keds could transmit Ca. Anaplasma camelii to small laboratory animals via blood-feeding. We show competence in pathogen transmission and subsequent infection in mice and rabbits by both direct detection in blood smears and subsequent molecular identification by PCR. Transmission of Ca. Anaplasma camelii to mice (8 - 47%) and rabbits (25%) occurred readily after ked bites. Hence, we demonstrate, for the first time, the potential of H. camelina as a vector of anaplasmosis. This key finding provides the basis for establishing ked control programmes for improvement of livestock and human health. Author summaryHematophagous flies such as Tabanids and Stomoxys, among other biting flies, are mechanical transmitters of various pathogens such as African trypanosomes and Anaplasma species. However, little is known about the role of common camel-specific biting keds (also known as camel flies or louse flies, genus Hippobosca) in pathogen transmission. Keds inflict painful bites to access host blood, and in the process may transmit bacterial hemopathogens frequently detected in both camels and their keds. We confirmed by experimental blood-feeding, gene amplification, and amplicon sequencing that camel keds can transmit "Candidatus Anaplasma camelii" from naturally-infected camels to healthy mice and rabbits. The high prevalence of camel anaplasmosis throughout the year in northern Kenya could be explained by the infestation camel-specific H. camelina, whose capacity as efficient fliers, unlike ticks, promotes disease transmission and maintenance within and among camel herds. Although this study focused on the transmission of Anaplasma sp. by camel keds, it is possible that other hemopathogens could also be transmitted by these flies through a similar mechanism. Notably, in the absence of their preferred hosts, keds occasionally bite humans and other vertebrates they come across in order to acquire bloodmeals, and in the process could transmit zoonotic pathogens.

microbiology↗