Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis–specific CD4⁺ T-cell response weakens the ability of macrophages to contain M. tuberculosis. We exposed peripheral blood mononuclear cells from M. tuberculosis–infected humans to schistosome soluble egg antigen (SEA) and then profiled M. tuberculosis–specific CD4⁺ T cells via multiparametric flow cytometry. SEA decreased the frequency of cells producing interferon γ (6.79% vs 3.20%; P = .017) and tumor necrosis factor α (6.98% vs 2.96%; P = .012), with a concomitant increase in the median fluorescence intensity of interleukin 4 (IL-4; P < .05) and interleukin 10 (IL-10; 1440 vs 1273; P < .05). Macrophages polarized with SEA-exposed, autologous CD4⁺ T-cell supernatant had a 2.19-fold decreased colocalization of lysosomes and M. tuberculosis (P < .05). When polarized with IL-4 or IL-10, macrophages had increased expression of CD206 (P < .0001), 1.5-fold and 1.9 fold increased intracellular numbers of M. tuberculosis per macrophage (P < .0005), and 1.4-fold and 1.7-fold decreased colocalization between M. tuberculosis and lysosomes (P < .001). This clarifies a relationship in which helminth-induced CD4⁺ T cells disrupt M. tuberculosis control by macrophages, thereby providing a mechanism for the observation that helminth infection advances the progression of tuberculosis among patients with M. tuberculosis infection.

Severe SARS-CoV-2 infection is associated with strong inflammation and autoantibody production against diverse self-antigens, suggesting a system-wide defect in B cell tolerance. BND cells are a B cell subset in healthy individuals harboring autoreactive but anergic B lymphocytes. In vitro evidence suggests inflammatory stimuli can breach peripheral B cell tolerance in this subset. We asked whether SARS-CoV-2–associated inflammation impairs BND cell peripheral tolerance. To address this, PBMCs and plasma were collected from healthy controls, individuals immunized against SARS-CoV-2, or subjects with convalescent or severe SARS-CoV-2 infection. We demonstrate that BND cells from severely infected individuals are significantly activated, display reduced inhibitory receptor expression, and restored BCR signaling, indicative of a breach in anergy during viral infection, supported by increased levels of autoreactive antibodies. The phenotypic and functional BND cell alterations significantly correlate with increased inflammation in severe SARS-CoV-2 infection. Thus, autoreactive BND cells are released from peripheral tolerance with SARS-CoV-2 infection, likely as a consequence of robust systemic inflammation.

Selective pressures generated by locomotor challenges act at the level of the individual. However, phenotypic variation among individuals that might convey a selective advantage may occur across any of multiple levels of biological organization. In this study, we test for differences in external morphology, muscle mechanical advantage, muscle fiber type and protein expression among individuals of the waterfall climbing Hawaiian fish Sicyopterus stimpsoni collected from sequential pools increasing in elevation within a single freshwater stream. Despite predictions from previous laboratory studies of morphological selection, few directional morphometric changes in body shape were observed at successively higher elevations. Similarly, lever arm ratios associated with the main pelvic sucker, central to climbing ability in this species, did not differ between elevations. However, among climbing muscles, the adductor pelvicus complex (largely responsible for generating pelvic suction during climbing) contained a significantly greater red muscle fiber content at upstream sites. A proteomic analysis of the adductor pelvicus revealed two-fold increases in expression levels for two respiratory chain proteins (NADH:ubiquinone reductase and cytochrome b) that are essential for aerobic respiration among individuals from successively higher elevations. Assessed collectively, these evaluations reveal phenotypic differences at some, but not all levels of biological organization that are likely the result of selective pressures experienced during climbing.

West Nile virus (WNV) is a single-stranded RNA flavivirus and is a major cause of viral encephalitis worldwide. Experimental models of WNV infection in mice are commonly used to define acute neuroinflammatory responses in the brain. Alpha-synuclein (Asyn) is a protein of primarily neuronal origin and is a major cause of Parkinson's disease (PD), a disorder characterized by loss of dopaminergic neurons. Both WNV and PD pathologies are largely mediated by inflammation of the central nervous system (neuroinflammation) and have overlapping inflammatory pathways. In this review, we highlight the roles of the immune system in both diseases while comparing and contrasting both protective and pathogenic roles of immune cells and their effector proteins. Additionally, we review the current literature showing that Asyn is an important mediator of the immune response with diverging roles in PD (pathogenic) and WNV disease (neuroprotective).

Although fathead minnows (Pimephales promelas) are commonly used as a model fish in endocrine disruption studies, past studies have not characterized sex-specific baseline expression of genes involved in sex differentiation during development in this species. Using a sex-linked DNA marker to verify gender, we evaluated the expression over time of genes involved in sex differentiation (dmrt1, cyp19a, cyp17, star, esr1, ar) in developing fathead minnows (10-45 days post hatch). Evaluation of these molecular markers in combination with gender identification help us to better understand the mechanisms regulating sex differentiation in fathead minnows and how endocrine-disrupting chemicals may alter these processes.