CD28 deficiency leads to accumulation of germinal-... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: PLoS One; v. 13, n. 8 AUG 27 2018.
Web of Science Citations: 2
Abstract

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)

FAPESP's process: 10/51150-4 - Animal model for analysis of the pathogenicity of Mycobacterium bovis strains and evaluation of cellular and humoral immune responses against pathogenic isolates
Grantee:Maria Regina D'Império Lima
Support Opportunities: Regular Research Grants
FAPESP's process: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis
Grantee:Maria Regina D'Império Lima
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 09/08559-1 - Characterization of effector mechanisms of innate and acquired immunity in chronic malaria model of CD28KO mice infected with Plasmodium chabaudi AS
Grantee:Henrique Borges da Silva
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/07140-2 - Role of inflammasomas in the pathogenesis of tuberculosis caused by hypervirulent clinical isolates of mycobacteria
Grantee:Maria Regina D'Império Lima
Support Opportunities: Regular Research Grants