The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice.

Details

Serval ID
serval:BIB_17B44C1E23A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice.
Journal
European Journal of Immunology
Author(s)
Charmoy M., Hurrell B.P., Romano A., Lee S.H., Ribeiro-Gomes F., Riteau N., Mayer-Barber K., Tacchini-Cottier F., Sacks D.L.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
2016
Volume
46
Number
4
Pages
897-911
Language
english
Abstract
Infection of C57BL/6 mice with most Leishmania major strains results in a healing lesion and clearance of parasites from the skin. Infection of C57BL/6 mice with the L. major Seidman strain (LmSd), isolated from a patient with chronic lesions, despite eliciting a strong Th1 response, results in a nonhealing lesion, poor parasite clearance, and complete destruction of the ear dermis. We show here that in comparison to a healing strain, LmSd elicited early upregulation of IL-1β mRNA and IL-1β-producing dermal cells and prominent neutrophil recruitment to the infected skin. Mice deficient in Nlrp3, apoptosis-associated speck-like protein containing a caspase recruitment domain, or caspase-1/11, or lacking IL-1β or IL-1 receptor signaling, developed healing lesions and cleared LmSd from the infection site. Mice resistant to LmSd had a stronger antigen-specific Th1 response. The possibility that IL-1β might act through neutrophil recruitment to locally suppress immunity was supported by the healing observed in neutropenic Genista mice. Secretion of mature IL-1β by LmSd-infected macrophages in vitro was dependent on activation of the Nlrp3 inflammasome and caspase-1. These data reveal that Nlrp3 inflammasome-dependent IL-1β, associated with localized neutrophil recruitment, plays a crucial role in the development of a nonhealing form of cutaneous leishmaniasis in conventionally resistant mice.
Keywords
IL-1 beta, Leishmaniasis, Nlrp3 inflammasome, Neutrophils, Skin
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2016 11:14
Last modification date
20/08/2019 12:47
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