Innate Lymphoid Cells in HIV/SIV Infections

Shah, Spandan V.; Manickam, Cordelia; Ram, Daniela; Reeves, R. Keith

doi:10.3389/fimmu.2017.01818

Cited by 18 publications

(17 citation statements)

References 113 publications

(136 reference statements)

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“…While samples were negatively gated for CD127 to exclude innate lymphoid cells, [20] inclusion of CD127 expression on NKB did not alter the immunological profile.…”

Section: Methodsmentioning

confidence: 99%

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract

Manickam

Nwanze

Ram

et al. 2018

Aids

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Objective Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in fact a subpopulation of B cells and exists in higher primates remains unclear. The objective of this study was to identify NKB cells in primates and study the impact of HIV/SIV infections. Design and Methods NKB cells were quantified in both naïve and lentivirus infected rhesus macaques and humans by excluding lineage markers (CD3, CD127), and positive Boolean gating for CD20, NKG2A/C and/or NKp46. Additional phenotypic measures were conducted by RNA-probe and traditional flow cytometry. Results Circulating cytotoxic NKB cells were found at similar frequencies in humans and rhesus macaques (range, 0.01 to 0.2% of total lymphocytes). NKB cells were notably enriched in spleen (median, 0.4% of lymphocytes), but were otherwise systemically distributed in tonsil, lymph nodes, colon, and jejunum. Expression of immunoglobulins was highly variable, but heavily favoured IgM and IgA rather than IgG. Interestingly, NKB cell frequencies expanded in PBMC and colon during SIV infection, as did IgG expression, but were generally unaltered in HIV-infected human subjects. Conclusion These results suggest a cell type expressing both NK and B cell features exists in rhesus macaques and humans and are perturbed by HIV/SIV infection. The full functional niche remains unknown, but the unique phenotype and systemic distribution could make NKB cells unique targets for immunotherapeutics or vaccine strategies.

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“…While samples were negatively gated for CD127 to exclude innate lymphoid cells, [20] inclusion of CD127 expression on NKB did not alter the immunological profile.…”

Section: Methodsmentioning

confidence: 99%

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract

Manickam

Nwanze

Ram

et al. 2018

Aids

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“…Notably, ILC3 depletion in HIV/SIV infection does not appear to be due to direct viral infection [ 130 , 136 ]. Rather, mechanistic studies have suggested that ILC3 depletion is the result of apoptosis, possibly due to dysregulation of ILC survival signals [ 137 ]. As such, analysis of ILC3 from humans with HIV-1 viremia shows upregulation of genes linked to apoptosis and cell death, including CD95 (Fas) [ 130 ].…”

Section: Loss Of Tolerance: Dysregulated Ilc3 Responses In Human Disementioning

confidence: 99%

Orchestration of intestinal homeostasis and tolerance by group 3 innate lymphoid cells

2018

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The gastrointestinal tract is the primary site of exposure to a multitude of microbial, environmental, and dietary challenges. As a result, immune responses in the intestine need to be tightly regulated in order to prevent inappropriate inflammatory responses to exogenous stimuli. Intestinal homeostasis and tolerance are mediated through a multitude of immune mechanisms that act to reinforce barrier integrity, maintain the segregation and balance of commensal microbes, and ensure tissue health and regeneration. Here, we discuss the role of group 3 innate lymphoid cells (ILC3) as key regulators of intestinal health and highlight how increasing evidence implicates dysregulation of this innate immune cell population in the onset or progression of a broad range of clinically relevant pathologies. Finally, we discuss how the next generation of immunotherapeutics may be utilized to target ILC3 in disease and restore gastrointestinal tolerance and tissue health.

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“…Specific immunological abnormalities within the GI tract are known to contribute directly to progressive HIV/SIV infections. T regulatory (T reg ) CD4 ϩ cells, Th17 cells, Tc17 cells, and innate lymphocyte type III (ILC3) cells are preferentially and persistently lost from the lamina propria of the GI tract in people living with HIV and in SIV-infected macaques and are not restored with the administration of ARVs (54)(55)(56). The loss of these cells and altered infiltration of neutrophils into GI tract tissues (57) contribute to epithelial barrier defects, microbial translocation, and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral Therapy Administration in Healthy Rhesus Macaques Is Associated with Transient Shifts in Intestinal Bacterial Diversity and Modest Immunological Perturbations

Ortiz

Flynn

DiNapoli

et al. 2019

J Virol

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Gastrointestinal (GI) immune system competency is dependent upon interactions with commensal microbiota, which can be influenced by wide-ranging pharmacologic interventions. In simian immunodeficiency virus (SIV)-infected Asian macaque models of human immunodeficiency virus (HIV) infection, we previously noted that initiation of antiretroviral therapy (ART) is associated with a specific imbalance (dysbiosis) of the composition of the intestinal bacteriome. To determine if ART itself might contribute to dysbiosis or immune dysfunction, we treated healthy rhesus macaques with protease, integrase, or reverse transcriptase inhibitors for 1 to 2 or for 5 to 6 weeks and evaluated intestinal immune function and the composition of the fecal bacterial microbiome. We observed that individual antiretrovirals (ARVs) modestly altered intestinal T-cell proinflammatory responses without disturbing total or activated T-cell frequencies. Moreover, we observed transient disruptions in bacterial diversity coupled with perturbations in the relative frequencies of bacterial communities. Shifts in specific bacterial frequencies were not persistent posttreatment, however, with individual taxa showing only isolated associations with T-cell proinflammatory responses. Our findings suggest that intestinal bacterial instability and modest immunological alterations can result from ART itself. These data could lead to therapeutic interventions which stabilize the microbiome in individuals prescribed ART. IMPORTANCE Dysbiosis of the fecal microbiome is a common feature observed in ARV-treated people living with HIV. The degree to which HIV infection itself causes this dysbiosis remains unclear. Here, we demonstrate that medications used to treat HIV infection can influence the composition of the GI tract immune responses and its microbiome in the nonhuman primate SIV model.

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Innate Lymphoid Cells in HIV/SIV Infections

Cited by 18 publications

References 113 publications

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract

Orchestration of intestinal homeostasis and tolerance by group 3 innate lymphoid cells

Antiretroviral Therapy Administration in Healthy Rhesus Macaques Is Associated with Transient Shifts in Intestinal Bacterial Diversity and Modest Immunological Perturbations

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