Published online before print December 22, 2009
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*Mammalian Genetics Unit, Medical Research Council, Harwell, United Kingdom;
Department of Infection, Immunity and Inflammation, University of Leicester, United Kingdom; and
The Roslin Institute, University of Edinburgh, Scotland, United Kingdom
@ To whom correspondence should be addressed. E-mail: v.ripoll{at}har.mrc.ac.uk.
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-
B, and ERK 1/2 signaling pathways, resulting in reduced secretion of TNF-
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.
Key Words: mononuclear phagocytes pneumococci TLR9 host pathogen interaction