HIV-specific CD4+Th17 cells from HIV infected long-term non-progressors exhibit lower CTLA-4 expression and reduced apoptosis

Saxena, Vandana; Patil, A.A.; Tayde, R. S.; Bichare, Shubhangi; Chinchkar, Varsha; Bagul, Rajani; Godbole, Sheela; Thakar, Madhuri

doi:10.1016/j.imbio.2018.07.011

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…Recent studies show that viral-specific Th17 responses can develop during HIV/SIV infection. 53,54 In addition, a subset of Tregs with TIGIT coexpression can suppress Th17 responses 55 ; so a loss of SIV-specific Th17 cells coupled with an increase in Th17 and Treg immune exhaustion could also contribute to reduced viral control during cART.…”

Section: Discussionmentioning

confidence: 99%

Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques

O’Connor

Munson

Tunggal

et al. 2019

AIDS Research and Human Retroviruses

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Depletion of gut T helper 17 (Th17) cells during HIV infection leads to decreased mucosal integrity and increased disease progression. Conversely, T regulatory (Treg) cells may inhibit antiviral responses or immune activation. In HIV elite controllers, a balanced Th17/Treg ratio is maintained in the blood, suggesting a role for these responses in controlling inflammation and viral replication. HIV-infected individuals exhibit a range in responsiveness to combination antiretroviral therapy (cART). Given the link between the Th17/Treg ratio and HIV disease, we reasoned these responses may play a role in cART responsiveness. In this study, we investigated the relationship between the mucosal Th17/Treg ratio to acute simian immunodeficiency virus (SIV) viremia and the response to cART. Nineteen rhesus macaques were infected with highly pathogenic SIVDB670 virus and cART was initiated 6 weeks postinfection. Mucosal CD4 T cell subsets were assessed by intracellular cytokine staining in the colon and mesenteric lymph nodes. Higher baseline Th17/Treg ratios corresponded with increased acute SIV viremia. Th17/Treg ratios decreased during acute SIV infection and were not restored during cART, and this corresponded to increased gut immune activation (Ki67 +), markers of microbial translocation (sCD14), and T cell exhaustion (TIGIT +). Animals that maintained a more balanced mucosal Th17/Treg ratio at the time of cART initiation exhibited a better virological response to cART and maintained higher peripheral CD4 counts. These results suggest mucosal Th17 and Treg homeostasis influences acute viremia and the response to cART, a result that suggests therapeutic interventions that improve the Th17/Treg ratio before or during cART may improve treatment of HIV.

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Section: Discussionmentioning

confidence: 99%

Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques

O’Connor

Munson

Tunggal

et al. 2019

AIDS Research and Human Retroviruses

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“…The Th17/Treg ratio decay becomes severe at a late stage of HIV infection, with values ranging from 0.75 to 0.2. In contrast, data suggest that Th17/Treg balance may be preserved in long-term non-progressors and maintained at an average level in elite controllers (47,49). Tryptophan catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) could contribute to this difference in the Th17/Treg ratio (112).…”

Section: The Dynamic Of Th17/treg Balance During Hiv Infection and On...mentioning

confidence: 99%

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs

et al. 2022

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Among CD4+ T-cells, T helper 17 (Th17) cells play a sentinel role in the defense against bacterial/fungal pathogens at mucosal barriers. However, Th17 cells are also highly susceptible to HIV-1 infection and are rapidly depleted from gut mucosal sites, causing an imbalance of the Th17/Treg ratio and impairing cytokines production. Consequently, damage to the gut mucosal barrier leads to an enhanced microbial translocation and systemic inflammation, a hallmark of HIV-1 disease progression. Th17 cells’ expression of mucosal homing receptors (CCR6 and α4β7), as well as HIV receptors and co-receptors (CD4, α4β7, CCR5, and CXCR4), contributes to susceptibility to HIV infection. The up-regulation of numerous intracellular factors facilitating HIV production, alongside the downregulation of factors inhibiting HIV, helps to explain the frequency of HIV DNA within Th17 cells. Th17 cells harbor long-lived viral reservoirs in people living with HIV (PLWH) receiving antiretroviral therapy (ART). Moreover, cell longevity and the proliferation of a fraction of Th17 CD4 T cells allow HIV reservoirs to be maintained in ART patients.

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“…The median seropositivity period of LTNPs was 11 years (range 8-19 years). Progressors were defined as anti-retroviral treatment (ART)-naïve HIV-infected patients with a CD4 count between 300 and 500 cells/mm 3 , while LTNPs were asymptomatic HIV-infected individuals who were ART-naïve with a stable CD4 count of ≥500 cells for 7 or more years [66]. The study was approved by the institutional ethics committee and the study participants were enrolled in the study after obtaining their written informed consent.…”

Section: Study Samplesmentioning

confidence: 99%

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

Pawar,

Gokavi,

Wakhare

et al. 2023

Viruses

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HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined. Since the progressors showed a dysregulated TLR-mediated innate response, we investigated the role of TLR agonists in restoring the innate functions of the progressors. The stimulation of PBMCs with TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 and TLR9 agonist-ODN 2216 resulted in an increased expression of IFN-α, IFN-β and IL-6. Interestingly, the expression of IFITM3, BST-2, IFITM-3, IFI-16 was also increased upon stimulation with TLR3 and TLR7 agonists, respectively. To further understand the molecular mechanism involved, the role of miR-155 was explored. Increased miR-155 expression was noted among the progressors. MiR-155 inhibition upregulated the expression of TLR3, NF-κB, IRF-3, TNF-α and the APOBEC-3G, IFITM-3, IFI-16 and BST-2 genes in the PBMCs of the progressors. To conclude, miR-155 negatively regulates TLR-mediated cytokines as wel l as the expression of host restriction factors, which play an important role in mounting anti-HIV responses; hence, targeting miR-155 might be helpful in devising strategic approaches towards alleviating HIV disease progression.

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HIV-specific CD4+Th17 cells from HIV infected long-term non-progressors exhibit lower CTLA-4 expression and reduced apoptosis

Cited by 7 publications

References 26 publications

Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques

Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

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