Biology subjects

Cano, J.

Publications and source records attributed to Cano, J..

9 recordsLinked to original sources

bioRxiv2025

Long-term Reprogramming and Altered Ontogeny of Classical Monocytes Mediates Enhanced Lung Injury in Sepsis Survivor Mice

Patients who survive sepsis are predisposed to new hospitalizations for respiratory failure, but the underlying mechanisms are unknown. Using a murine model in which prior sepsis predisposes to enhanced lung injury, we previously discovered that classical monocytes persist in the lungs after long-term recovery from sepsis and exhibit enhanced cytokine expression after secondary challenge with intra-nasal lipopolysaccharide. Here, we hypothesized that immune reprogramming of post-sepsis monocytes and altered ontogeny predispose to enhanced lung injury. Monocyte depletion and/or adoptive transfer was performed three weeks and three months after sepsis. Monocytes from post-sepsis mice were necessary and sufficient for enhanced LPS-induced lung injury and promoted neutrophil degranulation. Prior sepsis enhanced JAK-STAT signaling and AP-1 binding in monocytes and shifted monocytes toward the neutrophil-like monocyte lineage. In human sepsis and/or pneumonia survivors, monocytes were predictive of 90-day mortality and exhibit transcriptional and proteomic neutrophil-like signatures. We conclude that sepsis reprograms monocytes into a pro-inflammatory phenotype and skews bone marrow progenitors and monocytes toward the neutrophil-like lineage, predisposing to neutrophil degranulation and lung injury.

immunology↗

bioRxiv2025

Maternal undernutrition exacerbates microbiota-driven growth stunting through pre and postnatal effects

Linear growth stunting due to undernutrition affects 20% of children under the age of five with far-reaching consequences, including increased susceptibility to infection and altered cognitive development. Current nutritional interventions are largely ineffective in rescuing linear growth. A significant proportion of stunting originates in utero; however, the mechanisms by which maternal undernutrition is transmitted between generations remain poorly characterized. Here we employed a gnotobiotic murine model of intergenerational undernutrition in which offspring are exposed to distinct microbial communities both in utero and after birth. We found that maternal undernutrition exacerbated offspring growth deficits in a microbiota-dependent manner. Maternal undernutrition also altered the offspring microbiome, increasing abundance of Enterococcus species and Escherichia coli. Cross-fostering demonstrated critical roles for the microbiota in growth during both gestation and early life. These findings emphasize the need to target both mother and child in the design of nutritional therapies for undernutrition.

microbiology↗

bioRxiv2023

Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition

Childhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to undernutrition has been linked to poor outcomes, and mothers who experience stunting are more likely to give birth to stunted children. Murine models that capture the intergenerational and multifactorial nature of undernutrition are critical to understanding the underlying biology of this disorder. Here we report a gnotobiotic mouse model of undernutrition using microbiota from human infants with healthy or stunted growth trajectories. Intergenerational transmission of microbiota from parents to offspring leads to the development of growth and immune features of undernutrition and enteropathy, including reduced linear growth, intestinal villus blunting and accumulation of intraepithelial lymphocytes. In contrast, colonization after weaning reduces sensitivity to detect changes driven by distinct microbial communities. Overall, these results suggest intergenerational colonization is a useful approach with which to investigate microbiota-dependent growth and immunity in early life.

microbiology↗

bioRxiv2023

Deciphering the role of brainstem glycinergic neurons during startle and prepulse inhibition

Prepulse inhibition (PPI) of the auditory startle response is the gold standard operational measure of sensorimotor gating. Affected by various neurological and neuropsychiatric illnesses, PPI also declines during aging. While PPI deficits are often associated with cognitive overload, attention impairments and motor dysfunctions, their reversal is routinely used in experimental systems for drug screening. Yet, the cellular and circuit-level mechanisms of PPI remain unclear, even under non-pathological conditions. Recent evidence shows that neurons located in the brainstem caudal pontine reticular nucleus (PnC) expressing the glycine transporter type 2 (GlyT2+) receive inputs from the central nucleus of the amygdala (CeA) and contribute to PPI via an uncharted pathway. Using tract-tracing and immunohistochemical analyses in GlyT2-eGFP mice, we reveal the neuroanatomical location of CeA glutamatergic neurons innervating GlyT2+ neurons. Our precise in vitro optogenetic manipulations coupled to field electrophysiological recordings demonstrate that CeA glutamatergic inputs do suppress auditory neurotransmission in PnC neurons but not via action on transmitter release from auditory afferents. Rather, our data is consistent with excitatory drive onto GlyT2+ neurons. Indeed, our PPI experiments in vivo demonstrate that optogenetic activation of GlyT2+ PnC neurons increases PPI and is sufficient to induce PPI, clarifying the crucial role of these neurons in young GlyT2-Cre mice. In contrast, in older GlyT2-Cre mice, PPI is reduced and not further altered by optogenetic inhibition of GlyT2+ neurons. We conclude that GlyT2+ PnC neurons innervated by CeA glutamatergic inputs are crucial for PPI and we highlight their reduced activity during the age-dependent decline in PPI. SIGNIFICANCE STATEMENTSensorimotor gating is a pre-attentive mechanism that declines with age and that is affected by neuropsychiatric and neurological disorders. Prepulse inhibition (PPI) of startle commonly measures sensorimotor gating to assess cognitive and motor symptoms and to screen drug efficacy. Yet, the neuronal mechanisms underlying PPI are still unresolved, limiting therapeutic advances. Here, we identify brainstem glycinergic neurons essential for PPI using tract tracing, in vitro electrophysiology and precise in vivo optogenetic manipulations during startle measurements in mice. Innervated by amygdala glutamatergic inputs, we show that these glycinergic neurons are essential and sufficient to induce PPI in young mice. In contrast, these neurons do not contribute to PPI in older mice. We provide new insights to the theoretical construct of PPI.

neuroscience↗

bioRxiv2021

Plasmodium falciparum and helminth coinfections increase IgE and parasite-specific IgG responses

Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites since they induce different immune profiles. We studied the effects of coinfections on the antibody profile in a cohort of 715 Mozambican children and adults using the Luminex technology with a panel of 16 antigens from P. falciparum and 11 antigens from helminths (Ascaris lumbricoides, hookworm, Trichuris trichiura, Strongyloides stercoralis and Schistosoma spp.) and measured antigen-specific IgG and total IgE responses. We compared the antibody profile between groups defined by P. falciparum and helminth previous exposure (based on serology) and/or current infection (determined by microscopy and/or qPCR). In multivariable regression models adjusted by demographic, socioeconomic, water and sanitation variables, individuals exposed/infected with P. falciparum and helminths had significantly higher total IgE and antigen-specific IgG levels, magnitude (sum of all levels) and breadth of response to both types of parasites compared to individuals exposed/infected with only one type of parasite (p[≤] 0.05). There was a positive association between exposure/infection to P. falciparum and exposure/infection to helminths or the number of helminth species, and vice versa (p[≤] 0.001). In addition, children coexposed/coinfected tended (p= 0.062) to have higher P. falciparum parasitemia than those single exposed/infected. Our results suggest that an increase in the antibody responses in coexposed/coinfected individuals may reflect higher exposure and be due to a more permissive immune environment to infection in the host. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/445753v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@a1dc3corg.highwire.dtl.DTLVardef@82128corg.highwire.dtl.DTLVardef@18fcd98org.highwire.dtl.DTLVardef@2d5bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Predicting the Environmental Suitability and Population at Risk of Podoconiosis in Africa

BackgroundPodoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa is uncertain. MethodsWe applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the suitability and human population at risk. ResultsIn Africa, environmental suitability for podoconiosis was predicted in 29 countries. By 2020, the total population in areas suitable for podoconiosis was estimated at 114.5 million people, (95% confidence interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units defined by WHO in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of IUs with high environmental suitability are located in Angola (80 IUs), Cameroon (170 IUs), the DRC (244 IUs), Ethiopia (495 IUs), Kenya (217 IUs), Uganda (116 IUs) and Tanzania (112 IUs). Of the 1,655 environmental suitable IUs, 960 (58.0%) require more detailed community-level mapping ConclusionsOur estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes.

ecology↗

bioRxiv2019

Measuring the spatial heterogeneity on the reduction of vaginal fistula burden in Ethiopia between 2005 and 2016

Vaginal fistula is a shattering maternal complication characterized by an anomalous opening between the bladder and/or rectum and vagina resulting in continuous leakage of urine or stool. Although prevalent in Ethiopia, its magnitude and distribution is not well studied. We used statistical mapping models using 2005 and 2016 Ethiopia Demographic Health Surveys data combined with a suite of potential risk factors to estimate the burden of vaginal fistula among women of childbearing age. The estimated number of women of childbearing age with lifetime and untreated vaginal fistula in 2016 were 72,533 (95% CI 38,235-124,103) and 31,961 (95% CI 11,596-70,309) respectively. These figures show reduction from the 2005 estimates: 98,098 (95% CI 49,819-170,737) lifetime and 59,114 (95% CI 26,580-118,158) untreated cases of vaginal fistula. The number of districts having more than 200 untreated cases declined drastically from 54 in 2005 to 6 in 2016. Our results show a significant subnational variation in the burden of vaginal fistula. Overall, between 2005 and 2016 there was substantial reduction in the prevalence of vaginal fistula in Ethiopia. Our results help guide local level tracking, planning, spatial targeting of resources and implementation of interventions against vaginal fistula.

bioinformatics↗

bioRxiv2019

Genome variation and population structure among 1,142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii

Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analysed whole genomes of 1,142 individual mosquitoes sampled from the wild in 13 African countries, and a further 234 individuals comprising parents and progeny of 11 lab crosses. The data resource includes high confidence single nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We used these data to analyse genetic population structure, and characterise genetic diversity within and between populations. We also illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance, and for accelerating research and development of new vector control tools.

genomics↗

bioRxiv2019

Domains of transmission and association of community, school, and household sanitation with soil-transmitted helminth infections among children in coastal Kenya

IntroductionFew studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) and estimated the association of sanitation in each domain with STH infection.\n\nMethodsUsing data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village, school, and household sanitation with STH infection.\n\nFindingsWe found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains.\n\nConclusionFindings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.\n\nAuthor SummaryInfection by whipworm and hookworm results from either ingestion of eggs or larvae or through skin exposure to larvae. These eggs and larvae develop in suitable soils contaminated with openly-deposited human faeces. Safe disposal of faeces should reduce transmission of these soil-transmitted helminths (STH), yet evidence of the impact of sanitation on STH transmission remains limited. We used data collected during a large, community-wide survey to measure prevalence of STH infections in coastal Kenya in 2015 to examine the relationship between sanitation conditions at home, school, and village and the presence of STH infection among 4,104 children who reported attending schools. We found that sanitation access at home and school sanitation coverage, but not the overall level of village sanitation coverage, was protective against hookworm infection. In contrast, only high village sanitation coverage, but not home or school sanitation, was protective against whipworm infection. Current STH control strategies emphasise periodic deworming through mass drug administration (MDA) of at-risk populations, including school-age children. Our findings highlight the need for continued efforts, alongside MDA, to extend access to good sanitation facilities at homes, schools, and across communities.

epidemiology↗