biostudies-literature00690Paidipally PCRDF GlobalNIAID NIH HHSNational Institutes of Health1323-1333https://www.ebi.ac.uk/biostudies/studies/S-EPMC6018723biostudies-literatureUnknown217(8)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.The Journal of infectious diseasesInterleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.PMC6018723AI123310A1085135AI120257R01 AI123310Vankayalapati RDevalraju KPValluri VLRadhakrishnan RKDhiman RTvinnereim ARTripathi DPaidipally PVan AVenkatasubramanian S69falseInterleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.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.2018-01-01T00:00:00Z2018 Mar2024-10-18T23:34:20.664Z2019-08-03T07:02:37ZS-EPMC60187232939015310.1093/infdis/jiy034