title: Macrophages from BALB/c and CBA/Ca mice differ in their cellular responses to Streptococcus pneumoniae.
abstract: In a mouse model of pneumonia caused by Streptococcus pneumoniae, differences in the timing and vigor of the host inflammatory response have been associated with susceptibility to invasive disease. BALB/c and CBA/Ca mice are known to be resistant and susceptible to acute pneumococcal disease, respectively. In this study, we have demonstrated that BMM from BALB/c and CBA/Ca mice differ in their expression and regulation of TLR9 in response to S. pneumoniae. We have also shown that BMM from CBA/Ca mice failed to fully activate p38, NF-kappaB, and ERK 1/2 signaling pathways, resulting in reduced secretion of TNF-alpha and CCL5 in response to this pathogen. In addition, we have established that S. pneumoniae induced significant cell death in BMM from CBA/Ca mice. These findings indicate that variations between the two strains are likely to reflect differences in macrophage responses to the pathogen.
authors.affiliation: Mammalian Genetics Unit, Medical Research Council, Harwell, Oxfordshire OX11 0RD, UK. v.ripoll@har.mrc.ac.uk
authors.forename: Vera M
authors.initials: VM
authors.lastname: Ripoll
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: Roger
authors.initials: R
authors.lastname: Cox
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: Paul
authors.initials: P
authors.lastname: Denny
mesh_terms: D000208:Acute Disease; D000818:Animals; D016923:Cell Death / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D016328:NF-kappa B; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases