1. Interleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.
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Paidipally, Padmaja, Tripathi, Deepak, Van, Abhinav, Radhakrishnan, Rajesh Kumar, Dhiman, Rohan, Venkatasubramanian, Sambasivan, Devalraju, Kamakshi P., Tvinnereim, Amy R., Valluri, Vijaya Lakshmi, and Vankayalapati, Ramakrishna
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INTERLEUKIN-21 , *KILLER cells , *T cells , *CELLULAR control mechanisms , *TUBERCULOSIS , *MYCOBACTERIUM tuberculosis , *TUBERCULOSIS microbiology , *ANIMAL experimentation , *COMPARATIVE studies , *CYTOKINES , *GENES , *INTERLEUKINS , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *MONOCYTES , *RESEARCH , *DNA-binding proteins , *EVALUATION research , *MONONUCLEAR leukocytes , *PHYSIOLOGY - Abstract
Background: In the current study, we determined the effects of interleukin (IL)-21 on human natural killer (NK) cells and monocyte responses during Mycobacterium tuberculosis (Mtb) infection.Methods: We found that Mtb stimulated CD4+ and NK T cells from healthy individuals with latent tuberculosis infection (LTBI+) are major sources of IL-21. CD4+ cells from tuberculosis patients secreted less IL-21 than did CD4+ cells from healthy LTBI+ individuals. Interleukin-21 had no direct effect on Mtb-stimulated monocytes.Results: Interleukin-21-activated NK cells produced interferon (IFN)-γ, perforin, granzyme B, and granulysin; lysed Mtb-infected monocytes; and reduced Mtb growth. Interleukin-21-activated NK cells also enhanced IL-1β, IL-18, and CCL4/macrophage-inflammatory protein (MIP)-1β production and reduced IL-10 production by Mtb-stimulated monocytes. Recombinant IL-21 (1) inhibited Mtb growth, (2) enhanced IFN-γ, IL-1β, IL-18, and MIP-1β, and (3) reduced IL-10 expression in the lungs of Mtb-infected Rag2 knockout mice.Conclusions: These findings suggest that activated T cells enhance NK cell responses to lyse Mtb-infected human monocytes and restrict Mtb growth in monocytes through IL-21 production. Interleukin-21-activated NK cells also enhance the immune response by augmenting IL-1β, IL-18, and MIP-1β production and reducing IL-10 production by monocytes in response to an intracellular pathogen. [ABSTRACT FROM AUTHOR]- Published
- 2018
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