Analysis of the Enigma of Leptospirosis Epidemics in Zalophus californianus: Seroprevalence as a Biomarker of Exposure and Persistence

For almost 50 years, researchers have documented the zoonotic disease leptospirosis, which infects mammalian hosts every three to five years. Their findings in attempting to describe the persistent and cyclical nature of this disease in California Sea Lions (Zalophus californianus; CSLs) are primarily centered around environmental factors. It is still unknown whether Leptospira spread and accumulate in the sea lion population or if it is a recurrent infection resulting from external reservoirs. The present study focuses on immune responsiveness and its role in CSL leptospirosis epidemics intertwined with environmental drivers of disease. I analyzed antibodies IgM, IgG, and avidity IgG (IgGU) in lepto-positive and non-lepto-positive yearlings, juveniles, sub-adults, and adults. I also analyzed these antibodies with respect to the fall, winter, spring and summer seasons as well as in outbreak years and non-outbreak years (which were also years of El Niño occurrences). I found that adult CSLs produced the lowest amount of IgM and IgG of all age classes suggesting their high likelihood of re-exposure. In general, between lepto-positive and non-lepto-positive individuals of all age classes, antibody production was lowest in individuals that were non-lepto-positive. Comparing antibody titers to one another depicted a positive correlation amongst all titers besides one anomaly in the juvenile data where IgM and IgGU had a negative relationship. This suggests that age class has a significant role in leptospirosis epidemics. Outbreak and El Niño years which are most conducive to Leptospira survival had greater amounts of IgG and IgGU in CSL samples than non-outbreak/El Niño years. However, this same trend did not exist with IgM titers in the yearling and juvenile age classes. This suggests that environmental sensitivity to leptospirosis infection in terms of IgM production is impacted by age more so than IgG and IgGU. Seasonal analysis yielded that IgM and IgG titers were highest in the winter and lowest in the spring and fall. IgGU on the other hand, was produced in greater amounts in the fall and summer seasons, agreeing with past research. Furthermore, environmental anomalies may be changing our knowledge of leptospirosis as the winter season may play more of a role in epidemics than it was previously found to. Longitudinal analysis depicted a general declining trend of IgM, IgG, and IgGU in all CSL individuals throughout leptospirosis persistence. Furthermore, longitudinal IgM and IgGU titers were found to have statistically similar patterns as time persists, both differing from longitudinal IgG titers patterns. This confirms past literature and its conclusion that IgM and IgGU function similarly in acting as a marker for distinguishing between primary and subsequent infections. Future research should consider examining a greater number of CSLs equally distributed between the four seasons to further explain seasonal deviation effecting leptospirosis epidemics. Additionally, future researchers should incorporate more than one region of CSL residence into analysis to eliminate varying environmental effects on the nature of leptospirosis persistence

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells

Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes

CD4 effector lymphocytes (T ) are traditionally classified by the cytokines they produce. To determine the states that T cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T ) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ. + eff eff eff H

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