Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

TLR3 is required for survival following Coxsackievirus B3 infection by driving T lymphocyte activation and polarization: The role of dendritic cells

Full text
Author(s):
Sesti-Costa, Renata [1] ; Santiago Francozo, Marcela Cristina [1, 2] ; Silva, Grace Kelly [1] ; Proenca-Modena, Jose Luiz [3] ; Silva, Joao Santana [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, Ribeirao Preto, SP - Brazil
[2] Ctr Expt & Clin Infect Res GmbH, TWINCORE, Inst Infect Immunol, Hannover - Germany
[3] Univ Campinas UNICAMP, Dept Genet Evolut & Bioagents, Inst Biol, Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 12, n. 10 OCT 3 2017.
Web of Science Citations: 5
Abstract

Type B coxsackievirus (CVB) is a common cause of acute and chronic myocarditis, meningitis and pancreatitis, often leading to heart failure and pancreatic deficiency. The polarization of CD4(+) T lymphocytes and their cytokine milieu are key factors in the outcome of CVB-induced diseases. Thus, sensing the virus and driving the adaptive immune response are essential for the establishment of a protective immune response. TLR3 is a crucial virus recognition receptor that confers the host with resistance to CVB infection. In the current study, we found that TLR3 expression in dendritic cells plays a role in their activation upon CVB3 infection in vitro, as TLR3-deficient dendritic cells up-regulate CD80 and CD86 to a less degree than WT cells. Instead, they up-regulated the inhibitory molecule PD-L1 and secreted considerably lower levels of TNF-alpha and IL-10 and a higher level of IL-23. T lymphocyte proliferation in co-culture with CVB3-infected dendritic cells was increased by TLR3-expressing DCs and other cells. Furthermore, in the absence of TLR3, the T lymphocyte response was shifted toward a Th17 profile, which was previously reported to be deleterious for the host. TLR3-deficient mice were very susceptible to CVB3 infection, with increased pancreatic injury and extensive inflammatory infiltrate in the heart that was associated with uncontrolled viral replication. Adoptive transfer of TLR3(+) dendritic cells slightly improved the survival of TLR-deficient mice following CVB3 infection. Therefore, our findings highlight the importance of TLR3 signaling in DCs and in other cells to induce activation and polarization of the CD4(+) T lymphocyte response toward a Th1 profile and consequently for a better outcome of CVB3 infection. These data provide new insight into the immune-mediated mechanisms by which CVBs are recognized and cleared in order to prevent the development of myocarditis and pancreatitis and may contribute to the design of therapies for enteroviral infections. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 12/20786-6 - Molecular mechanisms involved in dendritic cell differentiation and CD4+ t cells polarization that confer resistance to viral infection
Grantee:Renata Sesti Costa
Support type: Scholarships in Brazil - Post-Doctorate