Evaluation of the Role of stat3 in Antibody and TH17-Mediated Responses to Pneumococcal Immunization and Infection by Use of a Mouse Model of Autosomal Dominant Hyper-IgE Syndrome.

Infection and Immunity
K MoffittRichard Malley

Abstract

Loss-of-function mutations in the signal transducer and activator of transcription 3 gene (stat3) result in autosomal dominant hyper-IgE syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including frequent pneumococcal and staphylococcal pneumonias. stat3 mutations cause defective adaptive TH17 cellular responses, an immune mechanism believed to be critical for clearance of pneumococcal colonization and diminished antibody responses. Here we wished to evaluate the role of stat3 in the clearance of pneumococcal carriage and immunity using mice with a stat3 mutation recapitulating AD-HIES. We show here that naive AD-HIES mice have prolonged nasal carriage of pneumococcus compared to WT mice. Mutant and wild-type mice were then immunized with a pneumococcal whole-cell vaccine (WCV) that provides TH17-mediated protection against pneumococcal colonization and antibody-mediated protection against pneumonia and sepsis. WCV-immunized AD-HIES mice made significantly less pneumococcus-specific interleukin-17A (IL-17A) and antibody than WT mice. The WCV-elicited protection against colonization was abrogated in AD-HIES mice, but immunization with WCV still protected AD-HIES mice against aspiration pn...Continue Reading

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