title: Differences in innate immune responses correlate with differences in murine susceptibility to Chlamydia muridarum pulmonary infection.
abstract: We investigated the phenotypic basis for genetically determined differences in susceptibility and resistance to Chlamydia muridarum pulmonary infection using BALB/c and C57BL/6 mice. Following C. muridarum intranasal inoculation, the intensity of infection was very different between BALB/c and C57BL/6 beginning as early as 3 days post-infection. Intrapulmonary cytokine patterns also differed at early time-points (days 2 and 4) between these two strains of mice. The early recruitment of neutrophils to lung tissue was greater in BALB/c than in C57BL/6 mice and correlated with a higher number of inclusion forming units (IFU) of C. muridarum. At day 12 post-infection, BALB/c mice continued to demonstrate a greater burden of infection, significantly higher lung cytokine levels for tumour necrosis factor-alpha and interleukin-17 (IL-17) and a significantly lower level for interferon-gamma than did C57BL/6 mice. In vitro, bone-marrow-derived dendritic cells (BMDCs) from BALB/c mice underwent less functional maturation in response to C. muridarum infection than did BMDCs from C57BL/6 mice. The BMDCs of BALB/c mice expressed lower levels of activation markers (CD80, CD86, CD40 and major histocompatibility complex class II) and secreted less IL-12 and more IL-23 than BMDCs from C57BL/6 mice. Overall, the data demonstrate that the differences exhibited by BALB/c and C57BL/6 mice following C. muridarum pulmonary infection are associated with differences in early innate cytokine and cellular responses that are correlated with late differences in T helper type 17 versus type 1 adaptive immune responses.
authors.affiliation: British Columbia Centre for Disease Control, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Jiang
authors.forename: Caixia
authors.initials: C
authors.lastname: Shen
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Karuna P
authors.initials: KP
authors.lastname: Karunakaran
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D016207:Cytokines; D020381:Interleukin-17