Host protection from L. pneumophila infection requires activation of innate signaling pathways in bone marrow-derived cells. Bone marrow-chimeric mice were generated by irradiating wild-type (WT) mice and reconstituting them with donor bone marrow from either WT (WT>WT), MyD88-deficient (MyD88−/−>WT), or Rip2/MyD88-deficient (Rip2−/− MyD88−/−>WT) mice. Mice were given a low intranasal dose (4 × 104 CFU) of L. pneumophila ΔflaA. (A) Bacterial CFU in the lung and spleen was measured at 5 days postinfection for irradiated mice (open circles) receiving bone marrow from wild-type, MyD88−/−, or Rip2−/− MyD88−/− donor mice and for mice with the same genetic background as the donors (filled circles). (B) BALF from infected mice was assayed for IL-6. Each point represents data from a single mouse. The lines indicate the means calculated from data for each group of mice. *, P < 0.05; **, P < 0.01.