title: Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic Mycobacterium tuberculosis Infection.
abstract: We have reported that TLR2 is crucial for host resistance against chronic Mycobacterium tuberculosis infection; however, which cell types are key players in this response remain unknown. This led us to decipher the relative contribution of TLR2 on nonhematopoietic and hematopoietic cells in resistance against chronic M. tuberculosis infection in mice infected with M. tuberculosis Erdman. Consistent with our previous report, at 8 wk of infection, TLR2 knockout (TLR2KO)→TLR2KO bone marrow chimeric mice exhibited increased bacterial burden, disorganized accumulation of lymphocytes and mononuclear cells, and extensive pulmonary immunopathology compared with wild-type (WT)→WT chimeric mice. Bacterial burden and pulmonary immunopathology of chimeric mice lacking TLR2 in the hematopoietic compartment (TLR2KO→WT) was comparable to TLR2KO mice. In contrast, chimeric mice deficient in TLR2 in the nonhematopoietic compartment (WT→TLR2KO) exhibited a marked attenuation in granulomatous inflammation compared with WT mice. Although the latter mice did not exhibit improved pulmonary bacterial control, significant reductions in bacterial burden in the draining lymph nodes, spleen, and liver were observed. These findings establish that the TLR2-mediated hematopoietic response promotes stable control of pulmonary bacterial burden and granuloma integrity, whereas TLR2 signaling on nonhematopoietic cells may partly facilitate granulomatous inflammation and bacterial dissemination.
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Jill
authors.initials: J
authors.lastname: Konowich
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
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 07101; and.
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 07101; and.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Ogilvy CommonHealth Worldwide, Parsippany, NJ 07054.
authors.forename: Wasiulla
authors.initials: W
authors.lastname: Rafi
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ 07101; and salgampa@njms.rutgers.edu.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D060888:Real-Time Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology*
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2