Cooperative signaling between multiple pattern recognition systems is important for a protective immune response against L. pneumophila. Rip2−/−, MyD88−/−, and Rip2−/− MyD88−/− mice in a C57BL/6 background were given a high intranasal dose (1 × 106 CFU) of either wild-type L. pneumophila or L. pneumophila ΔflaA. (A) At day 5 postinfection bacterial CFU were measured in the lung. Data in the left panel (day 0) represent CFU measured in the lungs of control animals sacrificed 4 h after intranasal infection. Each point represents data from a single mouse. The lines indicate the means calculated from the data for the two groups of mice. The dashed line indicates the lower limit of detection. *, P < 0.05 (B) The graph on the left indicates the survival of Rip2−/−, MyD88−/−, and Rip2−/− MyD88−/− mice after a high intranasal dose (1 × 106 CFU) of wild-type L. pneumophila (n = 9 mice for each group). The difference between the MyD88−/− and Rip2−/− MyD88−/− mice was significant (P < 0.01). The graph on the right shows the number of L. pneumophila bacteria in the lungs of mice surviving until day 21. (C) Survival of Rip2−/−, MyD88−/−, and Rip2−/− MyD88−/− mice after a high intranasal dose (1 × 106 CFU) of L. pneumophila ΔflaA (n = 3 mice for each group). The difference between the MyD88−/− and Rip2−/− MyD88−/− mice was significant (P < 0.05).