P.O. and Y.A.A. conceptualized the study and designed its experiments. P.O., S.H., and Y.A.A. performed all experiments. S.H. and M.K.B. performed IL-2 ELISA experiments. P.O. performed reanalysis of CyTOF data. S.H. performed analysis of TCGA data. S.G. managed all mouse work and genotyped and bred mice. A.A. assisted in experimental design and provided funding. P.O. wrote the manuscript, and all authors assisted in editing the manuscript. Y.A.A. supervised the study. The authorship order of the two cofirst authors was determined based on differing roles in conceptualization of the study and manuscript preparation. P.O. contributed mainly though design, planning, analysis, and writing of the manuscript, while S.H. physically performed many of the experiments and performed data analysis.

Current advances in combined anti-retroviral therapy (cART) have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The immune cell receptor SLAMF7 has been shown to be upregulated in diseases characterized by chronic immune activation. Here, we studied the function of the SLAMF7 receptor in immune cells of HIV patients and the impacts of SLAMF7 signaling on peripheral immune activation. We observed increased frequencies of SLAMF7+ PBMCs in HIV+ individuals in a clinical phenotype-dependent manner, with discordant and long-term nonprogressor patients showing elevated SLAMF7 levels, and elite controllers showing levels comparable to healthy controls. We also noted that SLAMF7 was sensitive to IFN⍺ stimulation; a factor elevated during HIV infection. Further studies revealed SLAMF7 to be a potent inhibitor of the monocyte-derived proinflammatory chemokine CXCL10 (IP-10) and other CXCR3 ligands, except in a subset of HIV+ patients termed SLAMF7 silent (SF7S). Studies utilizing small molecule inhibitors revealed that the mechanism of CXCL10 inhibition is independent of known SLAMF7 binding partners. Furthermore, we determined that SLAMF7 activation on monocytes is able to decrease their susceptibility to HIV-1 infection in vitro via down-regulation of CCR5 and up-regulation of the CCL3L1 chemokine. Finally, we discovered that neutrophils do not express SLAMF7, are CXCL10+ at baseline, are able to secrete CXCL10 in response to IFN⍺ and LPS, and are non-responsive to SLAMF7 signaling. These findings implicate the SLAMF7 receptor as an important regulator of IFN⍺-driven innate immune responses during HIV infection.

The deadly pandemic caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents one of the greatest threats humanity has faced in the last century. Infection with this easily transmissible virus can run the gamut from asymptomatic to fatal, and the disease caused by SARS-CoV-2 has been termed Coronavirus Disease 2019 (COVID-19). What little research that has already been conducted implicates pathological responses by the immune system as the leading culprit responsible for much of the morbidity and mortality caused by COVID-19. In this review we will summarize what is currently known about the systemic immune response to SARS-CoV-2 and potential immunotherapeutic approaches.

Ankylosing spondylitis (AS) is a prototypical sero-negative autoimmune disease that affects millions worldwide. Single nucleotide polymorphisms in the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) gene have been linked to AS via GWAS studies, however, the exact mechanism as to how ERAP1 contributes to pathogenesis of AS is not understood. We undertook µCT imaging and histologic analysis to evaluate bone morphology of the axial skeletons of ERAP1−/− mice and discovered the hallmark skeletal features of AS in these mice, including spinal ankylosis, osteoporosis, and spinal inflammation. We also confirmed the presence of spontaneous intestinal dysbiosis and increased susceptibility to Dextran Sodium Sulfate (DSS)-induced colitis in ERAP1−/− mice, however the transfer of healthy microbiota from wild type mice via cross-fostering experiments did not resolve the skeletal phenotypes of ERAP1−/− mice. Immunological analysis demonstrated that while ERAP1−/− mice had normal numbers of peripheral Foxp3+ Tregs, they had reduced numbers of both “Tr1-like” regulatory T cells and tolerogenic dendritic cells, which are important for Tr1 cell differentiation. Together, our data suggests that ERAP1−/− mice may serve as a useful animal model for studying pathogenesis of intestinal, skeletal, and immunological manifestations of Ankylosing Spondylitis.

Anaerobiospirillum succiniciproducens is a little-known spiral bacterium. Presented here are two septicemia cases similar in that both occurred in rural northern Virginia, both patients presented with dental infection, and in both cases the organism was first suspected to be Campylobacter. The morphology, motility, biochemical, and growth characteristics of Anaerobiospirillum are further defined.