CD28 deficiency leads to accumulation of germinal-center independent IgM(+) experienced B cells and to production of protective IgM during experimental malaria

Autor(es)

da Silva, Henrique Borges ^{[1, 2]} ; de Salles, Erika Machado ^[2] ; Lima-Mauro, Eliana Faquim ^[3] ; Sardinha, Luiz Roberto ^[4] ; Alvarez, Jose Maria ^[2] ; D'Imperio Lima, Maria Regina ^[2]

Afiliação do(s) autor(es)

^[1] Univ Minnesota, Dept Lab Med & Pathol, Ctr Immunol, Minneapolis, MN 55455 - USA

^[2] Univ Sao Paulo, ICB, Dept Imunol, Sao Paulo - Brazil

^[3] Inst Butantan, Lab Imunopatol, Sao Paulo - Brazil

^[4] Inst Israelite Ensino & Pesquisa Albert Einstein, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 13, n. 8 AUG 27 2018.
• Citações Web of Science: 2

Resumo

Protective immunity to blood-stage malaria is attributed to Plasmodium-specific IgG and effector-memory T helper 1 (Th1) cells. However, mice lacking the costimulatory receptor CD28 (CD28KO) maintain chronic parasitemia at low levels and do not succumb to infection, suggesting that other immune responses contribute to parasite control. We report here that CD28KO mice develop long-lasting non-sterile immunity and survive lethal parasite challenge. This protection correlated with a progressive increase of anti-parasite IgM serum levels during chronic infection. Serum IgM from chronically infected CD28KO mice recognize erythrocytes infected with mature parasites, and effectively control Plasmodium infection by promoting parasite lysis and uptake. These antibodies also recognize autoantigens and antigens from other pathogens. Chronically infected CD28KO mice have high numbers of IgM(+) plasmocytes and experienced B cells, exhibiting a germinal-center independent Fas(+)GL7(-)CD38(+)CD73(-) phenotype. These cells are also present in chronically infected C57BL/6 mice although in lower numbers. Finally, IgM(+) experienced B cells from cured C57BL/6 and CD28KO mice proliferate and produce anti-parasite IgM in response to infected erythrocytes. This study demonstrates that CD28 deficiency results in the generation of germinal-center independent IgM(+) experienced B cells and the production of protective IgM during experimental malaria, providing evidence for an additional mechanism by which the immune system controls Plasmodium infection. (AU)

• Processo FAPESP: 10/51150-4 - Modelo animal para análise da patogenicidade de cepas de Mycobacterium bovis e avaliação da resposta imune celular e humoral contra isolados patogênicos
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/20432-8 - Intervenção em vias de sinalização associadas ao reconhecimento de dano celular visando reduzir a patologia das formas graves de malária e tuberculose
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/08559-1 - Caracterização dos mecanismos efetores da imunidade inata e adquirida no modelo de malária crônica em camundongos CD28KO infectados pelo Plasmodium chabaudi AS
• Beneficiário: Henrique Borges da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/07140-2 - Papel dos inflamassomas na patogenia da tuberculose causada por isolados clínicos hipervirulentos de micobactérias
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular