title: CD27 contributes to the early systemic immune response to Mycobacterium tuberculosis infection but does not affect outcome.
abstract: The development of a strong Th1-mediated adaptive immune response is considered of main importance for host defense against the intracellular pathogen Mycobacterium tuberculosis. The induction of a cellular immune response is not only dependent on the engagement of the TCR but also requires co-stimulation. In order to study the role of the co-stimulatory molecule of the tumor necrosis factor receptor family member CD27 during murine M. tuberculosis infection, we intranasally infected wild-type (WT) and CD27 knockout (KO) mice with 10(5) colony-forming units M. tuberculosis. Whereas there were no differences in bacterial growth, inflammation and IFNgamma production by CD4+ and CD8+ lymphocytes in the lungs early after infection, the number of splenic CD8+ T cells producing the key Th1 cytokine IFNgamma was lower in CD27 KO mice than in WT mice. After 6 weeks, CD27 KO mice had 3.6-fold higher mycobacterial counts in their lungs and displayed more pulmonary inflammation and increased numbers of infiltrated leukocytes. Despite these differences early in infection, an equal number of WT and CD27 KO mice died during a 43-week observation period and lung bacterial loads and inflammation were comparable in the surviving animals. Our data suggest that CD27 does not contribute to the local IFNgamma-mediated response and long-term protection against M. tuberculosis.
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.wieland@amc.uva.nl
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Wieland
authors.forename: Marjolein E
authors.initials: ME
authors.lastname: Kerver
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Nolte
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
authors.forename: Rene
authors.initials: R
authors.lastname: van Lier
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7