Natural Killer Cell–Mediated Cytokine Response Among HIV-Positive South Indians With Pulmonary Tuberculosis

Rao, Pooja; Rajasekaran, S.; Raja, Alamelu

doi:10.1089/jir.2009.0018

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…These results reflect the interplay between pro-inflammatory and regulatory cytokines in TB/HIV patients and could indicate the establishment of regulatory mechanisms to control the exacerbated inflammatory response by the innate immune system in TB/HIV patients. Similar to our results, lower frequency of NK intracellular pro-inflammatory cytokines, IFN-γ and TNF-, were observed in TB/HIV patients from India compared to healthy controls (80).…”

Section: Discussionsupporting

confidence: 91%

“…Although NK cells regulate immune responses through cytokines secretion (79), there are few reports describing the NK regulatory cytokine secretion patterns in TB/HIV patients (80). In our study, TB/HIV patients showed a lower frequency of intracellular IFN-γ-producing NK cells compared to the HC group, as well as of TNF- compared to HIV, TB, and HC groups.…”

Section: Discussionmentioning

confidence: 99%

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Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

et al. 2019

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Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a ( p = 0.025), NKp80 ( p = 0.033), and NKG2C ( p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2–24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2 + /Vδ2 − ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6–24). An increase of CD161 + NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

et al. 2019

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“…Indeed, NK cells from individuals with HIV-1 and pulmonary tuberculosis failed to produce IFN-γ when stimulated in vitro with live M. tuberculosis . 81 Thus, understanding the mechanisms underlying HIV-1-associated NK cell dysfunction could aid in the development of therapies designed to enhance or restore innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

The Natural Killer Cell Interferon-Gamma Response to Bacteria Is Diminished in Untreated HIV-1 Infection and Defects Persist Despite Viral Suppression

Dillon

Lee

Bramante

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective Natural Killer (NK) cells are important in innate immune responses to bacterial as well as viral pathogens. HIV-1 infection is associated with opportunistic bacterial infections and with microbial translocation, but the nature of the NK cell response to bacteria during HIV infection has not been studied extensively. The objective of this study was to compare NK cell responses to bacteria in HIV-infected versus uninfected individuals. Methods Multi-color flow cytometry was used to evaluate the ability of blood NK cell subsets (CD56+CD16-, CD56+CD16+, and CD56-CD16+) from treated, virally suppressed and untreated viremic subjects with chronic HIV-1 infection, as well as uninfected controls, to secrete IFN-γ in response to in vitro stimulation of peripheral blood mononuclear cells with heat-killed commensal Escherichia coli or pathogenic Salmonella typhimurium. Results All three NK cell subsets produced IFN-γ in response to bacteria, but CD56-CD16+ NK cells were least responsive. Untreated HIV-1 infected donors had increased frequencies of CD56-CD16+ NK cells and lower overall frequencies of IFN-γ-producing NK cells responding to E. coli and S. typhimurium than NK cells from uninfected donors. These NK cell defects were not fully restored in ART-treated donors. Monocytes were necessary for NK cells to respond to bacteria, but the HIV-associated defect was intrinsic to NK cells since addition of normal monocytes did not restore IFN-γ production in response to bacteria. Conclusions Functional defects and numeric alterations of NK cell subsets lead to decreased frequencies of bacteria-reactive, IFN-γ-producing NK cells in HIV-1 infected subjects, even those on ART.

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“…IL-2–activated NK cells are known to increase the lytic activity compared with circulating NK cells and are able to lyse otherwise NK cell–resistant targets [10]. The potential effects of IL-15+ IL-12 on the enhancement of NK activity in HIV positive individuals have been demonstrated by us [8], [11], [12]. Hence, the present study assessed the effect of IL-15+ IL-12 on the expression of NK surface receptors in HIV positive individuals with and without TB co-infection.…”

Section: Introductionmentioning

confidence: 99%

Effect of Recombinant Cytokines on the Expression of Natural Killer Cell Receptors from Patients with TB or/and HIV Infection

2012

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BackgroundNK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients. The effect of IL-15+IL-12 stimulation on the expression of NK receptors was also studied.Methodology/Principal FindingsThe study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals and patients with HIV and tuberculosis co-infection. The expression of NK cell receptors was analyzed on two NK cell subsets within the peripheral blood: CD16+CD3− and CD56+CD3− using flow cytometry. The expression of inhibitory receptors (CD158a, CD158b, KIRp70, CD85j and NKG2A) on NK subsets was increased in HIV, when compared to NHS. But the response in HIV-TB was not uniform. Stimulation with IL-15+IL-12 dropped (p<0.05) the expression of CD85j and NKG2A in HIV. The basal expression of natural cytotoxicity receptors (NKp30 and NKp46) on NK cell subsets was lowered (p<0.05) in HIV and HIV-TB as compared to NHS. However, the expression of NKp44 and NKG2D was elevated in HIV. Enhanced NKp46 and NKG2D expression was observed in HIV with IL-15+IL-12 stimulation. The coreceptor NKp80 was found to be expressed in higher numbers on NK subsets from HIV compared to NHS, which elevated with IL-15+IL-12 stimulation. The expression of NK receptors and response to stimulation was primarily on CD56+CD3− subset.Conclusions/SignificanceIL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals viz down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. IL-15+IL-12 is not likely to be of value when co-infected with TB probably due to the influence of tuberculosis.

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Natural Killer Cell–Mediated Cytokine Response Among HIV-Positive South Indians With Pulmonary Tuberculosis

Cited by 8 publications

References 25 publications

Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

The Natural Killer Cell Interferon-Gamma Response to Bacteria Is Diminished in Untreated HIV-1 Infection and Defects Persist Despite Viral Suppression

Effect of Recombinant Cytokines on the Expression of Natural Killer Cell Receptors from Patients with TB or/and HIV Infection

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