Fernandes, Vitor E.Ercoli, GiuseppeBénard, AlanBrandl, CarolinFahnenstiel, HannahMüller-Winkler, JenniferWeber, Georg F.Denny, PaulNitschke, LarsAndrew, Peter W.2020-09-022020-09-0220201553-7366http://hdl.handle.net/10400.1/14668Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.engAnimalsB-LymphocytesBacteremiaFemaleHost-Pathogen InteractionsHumansMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAPneumococcal InfectionsPneumonia, PneumococcalSialic Acid Binding Ig-like Lectin 2Streptococcus pneumoniaejournal article10.1371/journal.ppat.1008464