Biology subjects

Shannon, J.

Publications and source records attributed to Shannon, J..

4 recordsLinked to original sources

bioRxiv2026

Polycyclic aromatic hydrocarbons, gut microbiome composition, impulsivity, and attention covary in a human cohort

Polycyclic aromatic hydrocarbons (PAHs) are pervasive environmental pollutants linked to adverse neurobehavioral outcomes, yet the biological pathways coupling exposure to behavior are poorly defined. The gut microbiome is both sensitive to PAH exposure and a modulator of central nervous system function, suggesting it may mediate how PAH exposure influences neurobehavior. We tested whether PAH exposure, gut microbiome composition, and neurobehavioral function covary in a statewide sample of 34 adults stratified into high-impulsivity/poor-attention (HH) and low-impulsivity/fast-attention (LL) groups. Participants provided fecal samples for 16S rRNA profiling and wore silicone wristbands for 30 days to passively sample PAH exposure. Higher PAH exposure associated with HH group membership in a sex-dependent manner, with the largest elevations among HH males. At the community level, PAH exposure profiles correlated with microbiome dissimilarity, and HH membership associated with increased alpha-diversity and altered community composition relative to LL members. At the taxon level, 21 genera were significantly associated with 14 PAH compounds (FDR < 0.1). No individual genera were significantly associated with neurobehavioral group after multiple testing correction. Nevertheless, cross-referencing PAH-responsive genera (FDR < 0.1) against those with nominal neurobehavioral associations (p < 0.05) identified two candidate genera, Hydrogenoanaerobacterium and Methanobrevibacter, whose abundance covaries with both PAH exposure and neurobehavioral phenotype. Both have been independently linked to cognitive or neurological outcomes in prior work. These findings support a three-way relationship among environmental chemical exposure, gut microbiome composition, and neurobehavioral function, establishing an empirical foundation for testing microbiome-mediated links between PAH exposure and neurobehavioral outcomes. IMPORTANCEPAH exposure is widespread and associates with impulsivity and attention problems, but how exposure translates into neurobehavioral risk is unclear. The gut microbiome is a plausible intermediary: gut microbes biotransform environmental chemicals and produce metabolites that influence brain function. In a statewide adult cohort, we show that higher PAH exposure tracks with greater impulsivity and poorer attention in a sex-dependent manner, and that both PAH exposure and neurobehavioral phenotype associate with distinct gut microbiome features at the community and taxon levels. We identify candidate genera at the intersection of PAH exposure and neurobehavioral group whose biology independently implicates them in cognitive and neurological function. By demonstrating that all three domains covary within a single human cohort, this work moves beyond pairwise associations to identify candidate microbial intermediaries for mechanistic investigation. Defining the microbiome constituents that respond to PAH exposure and co-associate with neurobehavioral phenotypes creates opportunities to test microbiome-targeted or exposure-reduction strategies for mitigating PAH-related neurobehavioral impacts.

microbiology↗

bioRxiv2023

An Aging-Susceptible Circadian Rhythm Controls Cutaneous Antiviral Immunity

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced antiviral proteins (AVPs) and circadian regulators including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin and such circadian-control of AVPs was diminished by disruption of immune cell interleukin 27 signaling and deletion of Bmal1/Clock genes in mouse skins, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment of circadian enhancing agents, nobiletin and SR8278, reduced infection of herpes simplex virus 1 (HSV1) in epidermal explants and human keratinocytes in a Bmal1/Clock-dependent manner. Circadian enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

immunology↗

bioRxiv2022

Zika virus spreads through infection of lymph node-resident macrophages

Zika virus (ZIKV) is an arthopod-vectored flavivirus that disseminates from the infection site into peripheral tissues, where it can elicit virus-induced pathology. To move through the body, ZIKV is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, multiple distinct steps during viral spread culminate in peripheral tissue infection, and the timing and mechanisms underlying mobile immune cell shuttling of virus remain unclear. To understand the very early steps in ZIKV dissemination from the skin, we kinetically and spatially mapped ZIKV-infected lymph nodes (LNs), an intermediary stop en route to the blood. Contrary to dogma, migratory immune cells were not required for large quantities of virus to reach the LN or blood. Instead, ZIKV rapidly infected a subset of immobile macrophages in the LN, which shed virus through the lymphatic pathway into the blood. Importantly, infection of LN macrophages alone was sufficient to initiate viremia. Together, our studies indicate that sessile macrophages that live and die in the LN contribute to initial ZIKV spread to the blood. These data build a more complete picture of ZIKV movement through the body and identify an alternate anatomical site for potential antiviral intervention. HighlightsO_LIZIKV infects and replicates in distinct LN macrophage populations C_LIO_LILN macrophage infection results in infectious virus in the blood C_LIO_LIVirus reaches the blood in the absence of DC migration or monocyte infection C_LIO_LINodal macrophage infection does not sustain viremia or induce morbidity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=74 HEIGHT=200 SRC="FIGDIR/small/508424v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@121bc33org.highwire.dtl.DTLVardef@1caf24borg.highwire.dtl.DTLVardef@e94a08org.highwire.dtl.DTLVardef@1fb6f62_HPS_FORMAT_FIGEXP M_FIG Caption: ZIKV infects lymph node macrophages, which shed infectious virus into the lymph and then blood. C_FIG

microbiology↗

bioRxiv2018

Influenza A Virus Negative Strand RNA is Translated for CD8+ T Cell Immunosurveillance

To probe the limits of CD8+ T cell immunosurveillance, we inserted the model peptide SIINFEKL into influenza A virus (IAV) negative strand gene segments. Although IAV genomic RNA is widely considered as non-coding, there is a conserved, relatively long open reading frame present in the genomic strand of segment eight, encoding a potential protein termed NEG8. The biosynthesis of NEG8 from IAV has yet to be demonstrated. While we failed to detect NEG8 protein expression in IAV infected cells, cell surface Kb-SIINFEKL complexes are generated when SIINFEKL is genetically appended to the predicted COOH-terminus of NEG8, as shown by activation of OT-I T cells in vitro and in vivo. Moreover, recombinant IAV encoding SIINFEKL embedded in the negative strand of the NA-stalk coding sequence also activates OT-I T cells in vivo. Together, our findings demonstrate both the translation of sequences on the negative strand of a single stranded RNA virus and its relevance anti-viral immunosurveillance.\n\nSignificanceEvery gene encodes complementary information on the opposite strand that can potentially be used for immunosurveillance. In this study, we show that the influenza A virus \"non-coding\" strand translated into polypeptides during a viral infection of either cultured cells or mice that can be recognized by CD8+ T cells. Our findings raise the possibility that influenza virus uses its negative strand to generate proteins useful to the virus. More generally, it adds to a growing literature showing that immunosurveillance extends to gene sequences generally thought not to be converted into proteins. The relevance of translating this \"dark\" information extends from viral immunity to cancer immunotherapy and autoimmunity.

immunology↗