title: Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection.
abstract: The present study tested the hypothesis that the scavenger receptor SR-A modulates granuloma formation in response to pulmonary infection with Mycobacterium tuberculosis (MTB). To test this hypothesis, we monitored survival and histopathology in WT and SR-A-deficient mice following aerosol infection with MTB Rv. SR-A-deficient (SR-A-/-) mice infected with MTB survived significantly longer than WT mice; the mean survival of SR-A-/- mice exceeded 430 days compared to 230 days for WT mice. Early granuloma formation was not impaired in SR-A-/- mice. The extended survival of SR-A-/- mice was associated with 13- and 3-fold higher number of CD4+ lymphocytes and antigen presenting cells in SR-A-/- lungs compared to WT mice 280 after infection. The histopathology of chronically infected SR-A-/- lungs, however, was marked by abundant cholesterol clefts in parenchymal lesions containing infection in multinucleated giant cells. The present study indicates SR-A as a candidate gene of the innate immune system influencing the chronic phase of M. tuberculosis infection.
authors.affiliation: University of Texas Health Science Center at Tyler, The Center for Biomedical Research, 11937 US Highway 271, Tyler, TX 75708-3154, United States. zchroneos@hmc.psu.edu
authors.forename: Zvjezdana
authors.initials: Z
authors.lastname: Sever-Chroneos
authors.forename: Amy
authors.initials: A
authors.lastname: Tvinnereim
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Zissis C
authors.initials: ZC
authors.lastname: Chroneos
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002908:Chronic Disease; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D015726:Giant Cells / Q000473:pathology; D006099:Granuloma / Q000382:microbiology; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D016019:Survival Analysis; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D051117:Scavenger Receptors, Class A; D002784:Cholesterol
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