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Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection
Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines that are induced after Cryptococcus neoformans infection and activate the interleukin-1 receptor type I (IL-1RI). To establish the role of IL-1RI signaling in protection against cryptococcal infection, we analy...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780350/ https://www.ncbi.nlm.nih.gov/pubmed/29403476 http://dx.doi.org/10.3389/fimmu.2017.01987 |
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author | Shourian, Mitra Ralph, Ben Angers, Isabelle Sheppard, Donald C. Qureshi, Salman T. |
author_facet | Shourian, Mitra Ralph, Ben Angers, Isabelle Sheppard, Donald C. Qureshi, Salman T. |
author_sort | Shourian, Mitra |
collection | PubMed |
description | Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines that are induced after Cryptococcus neoformans infection and activate the interleukin-1 receptor type I (IL-1RI). To establish the role of IL-1RI signaling in protection against cryptococcal infection, we analyzed wild-type (WT) and IL-1RI-deficient (IL-1RI(−/−)) mice on the BALB/c background. IL-1RI(−/−) mice had significantly reduced survival compared to WT mice after intratracheal challenge with C. neoformans 52D. Microbiological analysis showed a significant increase in the lung and brain fungal burden of IL-1RI(−/−) compared to WT mice beginning at weeks 1 and 4 postinfection, respectively. Histopathology showed that IL-1RI(−/−) mice exhibit greater airway epithelial mucus secretion and prominent eosinophilic crystals that were absent in WT mice. Susceptibility of IL-1RI(−/−) mice was associated with significant induction of a Th2-biased immune response characterized by pulmonary eosinophilia, M2 macrophage polarization, and recruitment of CD4(+) IL-13(+) T cells. Expression of pro-inflammatory [IL-1α, IL-1β, TNFα, and monocyte chemoattractant protein 1 (MCP-1)], Th1-associated (IFNγ), and Th17-associated (IL-17A) cytokines was significantly reduced in IL-1RI(−/−) lungs compared to WT. WT mice also had higher expression of KC/CXCL1 and sustained neutrophil recruitment to the lung; however, antibody-mediated depletion of these cells showed that they were dispensable for lung fungal clearance. In conclusion, our data indicate that IL-1RI signaling is required to activate a complex series of innate and adaptive immune responses that collectively enhance host defense and survival after C. neoformans 52D infection in BALB/c mice. |
format | Online Article Text |
id | pubmed-5780350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57803502018-02-05 Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection Shourian, Mitra Ralph, Ben Angers, Isabelle Sheppard, Donald C. Qureshi, Salman T. Front Immunol Immunology Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines that are induced after Cryptococcus neoformans infection and activate the interleukin-1 receptor type I (IL-1RI). To establish the role of IL-1RI signaling in protection against cryptococcal infection, we analyzed wild-type (WT) and IL-1RI-deficient (IL-1RI(−/−)) mice on the BALB/c background. IL-1RI(−/−) mice had significantly reduced survival compared to WT mice after intratracheal challenge with C. neoformans 52D. Microbiological analysis showed a significant increase in the lung and brain fungal burden of IL-1RI(−/−) compared to WT mice beginning at weeks 1 and 4 postinfection, respectively. Histopathology showed that IL-1RI(−/−) mice exhibit greater airway epithelial mucus secretion and prominent eosinophilic crystals that were absent in WT mice. Susceptibility of IL-1RI(−/−) mice was associated with significant induction of a Th2-biased immune response characterized by pulmonary eosinophilia, M2 macrophage polarization, and recruitment of CD4(+) IL-13(+) T cells. Expression of pro-inflammatory [IL-1α, IL-1β, TNFα, and monocyte chemoattractant protein 1 (MCP-1)], Th1-associated (IFNγ), and Th17-associated (IL-17A) cytokines was significantly reduced in IL-1RI(−/−) lungs compared to WT. WT mice also had higher expression of KC/CXCL1 and sustained neutrophil recruitment to the lung; however, antibody-mediated depletion of these cells showed that they were dispensable for lung fungal clearance. In conclusion, our data indicate that IL-1RI signaling is required to activate a complex series of innate and adaptive immune responses that collectively enhance host defense and survival after C. neoformans 52D infection in BALB/c mice. Frontiers Media S.A. 2018-01-19 /pmc/articles/PMC5780350/ /pubmed/29403476 http://dx.doi.org/10.3389/fimmu.2017.01987 Text en Copyright © 2018 Shourian, Ralph, Angers, Sheppard and Qureshi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Shourian, Mitra Ralph, Ben Angers, Isabelle Sheppard, Donald C. Qureshi, Salman T. Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title | Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title_full | Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title_fullStr | Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title_full_unstemmed | Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title_short | Contribution of IL-1RI Signaling to Protection against Cryptococcus neoformans 52D in a Mouse Model of Infection |
title_sort | contribution of il-1ri signaling to protection against cryptococcus neoformans 52d in a mouse model of infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780350/ https://www.ncbi.nlm.nih.gov/pubmed/29403476 http://dx.doi.org/10.3389/fimmu.2017.01987 |
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