The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection

• Autor(a) principal: Fernandes, Vitor E.
• Data de Publicação: 2020
• Outros Autores: Ercoli, Giuseppe, Bénard, Alan, Brandl, Carolin, Fahnenstiel, Hannah, Müller-Winkler, Jennifer, Weber, Georg F., Denny, Paul, Nitschke, Lars, Andrew, Peter W.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/14668
• topic: Animals; B-Lymphocytes; Bacteremia; Female; Host-Pathogen Interactions; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Pneumococcal Infections; Pneumonia, Pneumococcal; Sialic Acid Binding Ig-like Lectin 2; Streptococcus pneumoniae

Streptococcus 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.