Enhanced susceptibility of mice infected with murine cytomegalovirus to intranasal challenge with Escherichia coli: pathogenesis and altered inflammatory response

Three-week-old mice inoculated intraperitoneally with murine cytomegalovirus (MCMV) and then challenged intranasally with Escherichia coli strain K1 demonstrated enhanced mortality (70%-90%) as compared with control animals infected with either pathogen alone (0-2007, P < 0.05). Mortality was greatest when animals were challenged with E. coli on days 1 or 3 after MCMV inoculation. On day 3 of infection with MCMV, clearance of E. coli from blood and tissues was impaired, and there was a decreased inflammatory response to an E. coli-inoculated sponge implanted subcutaneously (geometric mean of 830 leukocytes in sponge fluid/mm3 in MCMV-infected animals vs. 8,510 leukocytes/mm3 in controls, P< 0.01). On days 1 and 3 of MCMV infection, decreased leukocyte counts in sponge fluid correlated with increased levels of bacteremia (P < 0.05). These results indicate that MCMV enhances susceptibility to an intranasal challenge with E. coli. A decrease in the inflammatory response may be one mechanism by which MCMV increases susceptibility to bacterial infections. Several observations in humans and experimental animals indicate that infection with cytomegalovirus (CMV) enhances susceptibility to secondary infections. An increased frequency of bacterial or fungal infections occurs in transplant recipients with primary CMV infection [1, 2], and bacteremia has been associated with CMV viremia in