title: IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis.
abstract: Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M. tb). Using antibodies, short interfering RNA and gene-deleted mice, we found that expansion of memory-like NK cells depends on interleukin 21 (IL-21). NKp46+CD27+KLRG1+ NK cells expanded in healthy individuals with latent TB infection in an IL-21-dependent manner. Our study provides first evidence that memory-like NK cells survive long term, expansion depends on IL-21, and involved in vaccine-induced protective immunity against a bacterial pathogen.
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: S
authors.initials: S
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cheekatla
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Paidipally
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: E
authors.initials: E
authors.lastname: Welch
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Tvinnereim
authors.affiliation: Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: R
authors.initials: R
authors.lastname: Nurieva
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vankayalapati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D055985:Latent Tuberculosis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D014611:Vaccination; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D019138:Antibodies, Blocking; D007378:Interleukins; D034741:RNA, Small Interfering; D000098546:Interleukin-21