title: Vaccine-mediated immunity to experimental Mycobacterium tuberculosis is not impaired in the absence of Toll-like receptor 9.
abstract: Accumulating evidence indicates that inflammatory signals required for maximizing effector T cell generation have opposing effects on the development of memory T cell precursors. Toll-like receptor (TLR)2, and TLR9 significantly contribute to the inflammatory milieu and therefore in this study we examined whether the absence of TLR9 alone or the combined absence of TLR2 and TLR9 would affect vaccine-mediated immunity to Mtb. We found that TLR9KO and TLR2/9DKO mice vaccinated with a live Mtb auxotroph, akin to vaccinated WT mice, exhibited early control of Mtb growth in the lungs compared to their naïve counterparts. The granulomatous response, IFNγ production and cellular recruitment to the lungs were also similar in all the vaccinated groups of mice. These findings indicate that there is minimal contribution from TLR2 and TLR9 in generating memory immunity to Mtb with live vaccines. Defining the innate milieu that can drive maximal memory T cell generation with a tuberculosis vaccine needs further inquiry.
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA; Rutgers-Graduate School of Biomedical Sciences, Newark, NJ, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA; Rutgers-Graduate School of Biomedical Sciences, Newark, NJ, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Dietzold
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA. Electronic address: salgampa@njms.rutgers.edu.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D051217:Toll-Like Receptor 9; D014612:Vaccines
keywords: IL-12; Memory immunity; Mycobacterium tuberculosis; Toll-like receptor 9; Vaccination