Linking Hydrothermal Geochemistry to Organismal Physiology: Physiological Versatility in Riftia pachyptila from Sedimented and Basalt-hosted Vents

Much of what is known regarding Riftia pachyptila physiology is based on the wealth of studies of tubeworms living at diffuse flows along the fast-spreading, basalt-hosted East Pacific Rise (EPR). These studies have collectively suggested that Riftia pachyptila and its chemoautotrophic symbionts are physiologically specialized, highly productive associations relying on hydrogen sulfide and oxygen to generate energy for carbon fixation, and the symbiont's nitrate reduction to ammonia for energy and biosynthesis. However, Riftia also flourish in sediment-hosted vents, which are markedly different in geochemistry than basalt-hosted systems. Here we present data from shipboard physiological studies and global quantitative proteomic analyses of Riftia pachyptila trophosome tissue recovered from tubeworms residing in the EPR and the Guaymas basin, a sedimented, hydrothermal vent field. We observed marked differences in symbiont nitrogen metabolism in both the respirometric and proteomic data. The proteomic data further suggest that Riftia associations in Guaymas may utilize different sulfur compounds for energy generation, may have an increased capacity for energy storage, and may play a role in degrading exogenous organic carbon. Together these data reveal that Riftia symbionts are far more physiologically plastic than previously considered, and that -contrary to previous assertions- Riftia do assimilate reduced nitrogen in some habitats. These observations raise new hypotheses regarding adaptations to the geochemical diversity of habitats occupied by Riftia, and the degree to which the environment influences symbiont physiology and evolution

Longitudinal Assessment of the Enhanced Liver Fibrosis Score in the Era of Contemporary HIV and Hepatitis C Virus Treatment

BACKGROUND: The trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy. METHODS: We assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1-2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1-2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count). RESULTS: INSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment. CONCLUSIONS: The apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential

Treatment of immunocompromised COVID-19 patients with convalescent plasma.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19

MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity

<div><p>People with HIV infection are at increased risk for community-acquired methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA) skin and soft tissue infections (SSTIs). Lower CD4 T-cell counts, higher peak HIV RNA levels and epidemiological factors may be associated with increased risk but no specific immune defect has been identified. We aimed to determine the immunologic perturbations that predispose HIV-infected people to MRSA SSTIs. Participants with or without HIV infection and with MRSA SSTI, MRSA colonization or negative for MRSA were enrolled. Peripheral blood and skin biopsies from study participants were collected. Flow cytometry, flow cytometry with microscopy, multiplex assays of cell culture supernatants and immunohistochemistry were used to evaluate the nature of the immune defect predisposing HIV-infected people to MRSA infections. We found deficient MRSA-specific IFNγ⁺ CD4 T-cell responses in HIV-infected people with MRSA SSTIs compared to MRSA-colonized participants and HIV-uninfected participants with MRSA SSTIs. These IFNγ⁺ CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs. However, IFNγ responses to cytomegalovirus and <i>Mycobacterium avium</i> antigens and MRSA-specific IL-17 responses by CD4 T cells were intact. Upon stimulation with MRSA, peripheral blood mononuclear cells from HIV-infected participants produced less IL-12 and IL-15, key drivers of IFNγ production. There were no defects in CD8 T-cell responses, monocyte responses, opsonization, or phagocytosis of <i>Staphylococcus aureus</i>. Accumulation of CD3 T cells, CD4 T cells, IL-17⁺ cells, myeloperoxidase⁺ neutrophils and macrophage/myeloid cells to the skin lesions were similar between HIV-infected and HIV-uninfected participants based on immunohistochemistry. Together, these results indicate that MRSA-specific IFNγ⁺ CD4 T-cell responses are essential for the control of initial and recurrent MRSA infections in HIV-infected people.</p></div

MRSA-specific memory CD4 T cells.

<p>Flow cytometry analysis of MRSA-specific memory (CD27⁺CD45RO⁺ or CD27^-) CD4 T-cell responses in HIV-infected or HIV-uninfected participants with MRSA SSTI, colonization or neither. Frequency of memory CD4 T cells producing (A) IFNγ, (B) IL-17, (C) TNF and (D) CD40L. For all figures, horizontal lines indicate medians. <i>P</i>-values were calculated using the Mann-Whitney <i>U</i> test.</p

Baseline characteristics.

<p>Baseline characteristics.</p

Histological evaluation of skin biopsies.

<p>Skin biopsies were obtained from MRSA SSTI participants at the infection site (SSTI lesion) or a distant site (SSTI Not Lesion), or MRSA-negative participants (-). (A) Abundance of CD3. (B) Abundance of CD4. (C) Abundance of IL-17. (D) Abundance of neutrophils (myeloperoxidase⁺ [MPO]). (E) Abundance of macrophage/myeloid cells (CD68⁺ and/or CD163⁺). <i>P</i>-values were calculated using the Mann-Whitney <i>U</i> test.</p

Food Insecurity Is Associated With Inflammation Among Women Living With HIV

BackgroundChronic inflammation is associated with AIDS-defining and non-AIDS-defining conditions. Limited research has considered how food insecurity influences chronic inflammation among people living with human immunodeficiency virus (HIV). We examined whether food insecurity was associated with higher levels of inflammation among women living with HIV (WWH) in the United States.MethodsWe analyzed cross-sectional data collected in 2015 from 421 participants on antiretroviral therapy from the Women's Interagency HIV Study. The exposure was any food insecurity. The outcome was inflammation, measured by proinflammatory cytokine interleukin-6 (IL-6) and tumor necroses factor receptor 1 (TNFR1) levels. We conducted multivariable linear regressions, adjusting for sociodemographic, clinical, and nutritional factors.ResultsNearly one-third of participants (31%) were food insecure and 79% were virally suppressed (&lt;20 copies/mL). In adjusted analyses, food insecurity was associated with 1.23 times the level of IL-6 (95% confidence interval [CI], 1.06-1.44) and 1.13 times the level of TNFR1 (95% CI, 1.05-1.21). Findings did not differ by HIV control (virally suppressed with CD4 counts ≥500 cells/mm3 or not) in adjusted stratified analyses.ConclusionFood insecurity was associated with elevated inflammation among WWH regardless of HIV control. Findings support the need for programs that address food insecurity among WWH

Cytokine concentrations released into supernatant.

<p>Supernatant concentrations of IFNγ (A) and drivers of IFNγ production, IL-12 (B) and IL-15 (C), after MRSA stimulation of PBMCs were assayed using the Luminex platform. <i>P</i>-values were calculated using the Mann-Whitney <i>U</i> test.</p