Defective expansion and function of memory like natural killer cells in HIV+ individuals with latent tuberculosis infection

Tuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ indi...

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Veröffentlicht in:PloS one 2021-09, Vol.16 (9), p.e0257185-e0257185
Hauptverfasser: Devalraju, Kamakshi Prudhula, Neela, Venkata Sanjeev Kumar, Krovvidi, Siva Sai, Vankayalapati, Ramakrishna, Valluri, Vijaya Lakshmi
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container_title PloS one
container_volume 16
creator Devalraju, Kamakshi Prudhula
Neela, Venkata Sanjeev Kumar
Krovvidi, Siva Sai
Vankayalapati, Ramakrishna
Valluri, Vijaya Lakshmi
description Tuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized. In this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10. In freshly isolated PBMCs, percentages of CD3.sup.- CD56.sup.+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3.sup.- CD56.sup.+ CD16.sup.+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32[alpha], IL-15 and IFN-[gamma] in response to Mtb antigens in LTBI+ individuals. We studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-[gamma] and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.
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HIV infection also inhibited the expansion of memory like NK cells, production of IL-32[alpha], IL-15 and IFN-[gamma] in response to Mtb antigens in LTBI+ individuals. We studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-[gamma] and granzyme B and increased CCL5 production. 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The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized. In this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10. In freshly isolated PBMCs, percentages of CD3.sup.- CD56.sup.+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3.sup.- CD56.sup.+ CD16.sup.+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32[alpha], IL-15 and IFN-[gamma] in response to Mtb antigens in LTBI+ individuals. We studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-[gamma] and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34516566</pmid><doi>10.1371/journal.pone.0257185</doi><tpages>e0257185</tpages><orcidid>https://orcid.org/0000-0002-0462-4174</orcidid><oa>free_for_read</oa></addata></record>
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subjects Age groups
Antigens
Authorship
Biology and life sciences
Care and treatment
CD16 antigen
CD3 antigen
CD56 antigen
Cell activation
Cytokines
ESAT-6 antigen
Expansion
Granzyme B
Health aspects
Health care
Health risks
HIV
HIV infection
Human immunodeficiency virus
Immune system
Immunology
Infections
Infectious diseases
Interleukin 15
Killer cells
Lymphocytes
Lymphocytes T
Medical research
Medicine and health sciences
Molecular biology
Monocytes
Natural killer cells
Pathogens
Patients
Public health
Research and Analysis Methods
Tuberculosis
γ-Interferon
title Defective expansion and function of memory like natural killer cells in HIV+ individuals with latent tuberculosis infection
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