Resistance to mycobacterial infection: a pattern of early immune responses leads to a better control of pulmonary infection in C57BL/6 compared with BALB/c mice.
In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-gamma in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-alpha were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-gamma stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection.
Arko-Mensah
John
J
Department of Immunology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
Rahman
Muhammad J
MJ
Dégano
Irene R
IR
Chuquimia
Olga D
OD
Fotio
Agathe L
AL
Garcia
Irene
I
Fernández
Carmen
C
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma; D018664:Interleukin-12 / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma