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Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis.
PLoS Pathog 2019; 15(8):e1007990PP

Abstract

The granulomatous lesion resulting from infection with the fungus Paracoccidioides brasiliensis is characterized by a compact aggregate of mature cells, surrounded by a fibroblast- and collagen-rich content. Granuloma formation requires signaling elicited by inflammatory molecules such as members of the interleukin-1 family. Two members of this family have been thoroughly studied, namely IL-1α and IL-1β. In this study, we addressed the mechanisms underlying IL-1α secretion and its functional role on the host resistance to fungal infection. We found that, the expression of caspase-11 triggered by P. brasiliensis infection of macrophages depends on IFN-β production, because its inhibition reduced procaspase-11 levels. Curiously, caspase-11 deficiency did not impair IL-1β production, however caspase-11 was required for a rapid pore-mediated cell lysis. The plasma membrane rupture facilitated the release of IL-1α, which was necessary to induce NO production and restrict fungal replication. Furthermore, P. brasiliensis-infected macrophages required IL-1α to produce optimal levels of IL-6, a major component of Th17 lymphocyte differentiation. Indeed, IL-1α deficiency accounted for a significant reduction of Th17 lymphocytes in lungs of infected mice, correlating with diminished neutrophil infiltration in the lungs. Strikingly, we identified that IL-1α directly reprograms the transcriptional profile of Th17-committed lymphocytes, increasing cellular proliferation, as for boosting IL-17 production by these cells. Beyond neutrophil chemotaxis in vivo, IL-17 also amplified IL-1α production by infected macrophages in vitro, endorsing a critical amplification loop of the inflammatory response. Therefore, our data suggest that the IFN-β/caspase-11/IL-1α pathway shapes a protective antifungal Th17 immunity, revealing a molecular mechanism underlying the cross-talk between innate and adaptive immunity.

Authors+Show Affiliations

Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Fiocruz-Bi-Institutional Translational Medicine Project, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31425553

Citation

Ketelut-Carneiro, Natália, et al. "Caspase-11-dependent IL-1α Release Boosts Th17 Immunity Against Paracoccidioides Brasiliensis." PLoS Pathogens, vol. 15, no. 8, 2019, pp. e1007990.
Ketelut-Carneiro N, Souza COS, Benevides L, et al. Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis. PLoS Pathog. 2019;15(8):e1007990.
Ketelut-Carneiro, N., Souza, C. O. S., Benevides, L., Gardinassi, L. G., Silva, M. C., Tavares, L. A., ... Silva, J. S. (2019). Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis. PLoS Pathogens, 15(8), pp. e1007990. doi:10.1371/journal.ppat.1007990.
Ketelut-Carneiro N, et al. Caspase-11-dependent IL-1α Release Boosts Th17 Immunity Against Paracoccidioides Brasiliensis. PLoS Pathog. 2019;15(8):e1007990. PubMed PMID: 31425553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis. AU - Ketelut-Carneiro,Natália, AU - Souza,Camila Oliveira Silva, AU - Benevides,Luciana, AU - Gardinassi,Luiz Gustavo, AU - Silva,Maria Cláudia, AU - Tavares,Lucas Alves, AU - Zamboni,Dario Simões, AU - Silva,João Santana, Y1 - 2019/08/19/ PY - 2019/02/02/received PY - 2019/07/18/accepted PY - 2019/08/29/revised PY - 2019/8/20/pubmed PY - 2019/8/20/medline PY - 2019/8/20/entrez SP - e1007990 EP - e1007990 JF - PLoS pathogens JO - PLoS Pathog. VL - 15 IS - 8 N2 - The granulomatous lesion resulting from infection with the fungus Paracoccidioides brasiliensis is characterized by a compact aggregate of mature cells, surrounded by a fibroblast- and collagen-rich content. Granuloma formation requires signaling elicited by inflammatory molecules such as members of the interleukin-1 family. Two members of this family have been thoroughly studied, namely IL-1α and IL-1β. In this study, we addressed the mechanisms underlying IL-1α secretion and its functional role on the host resistance to fungal infection. We found that, the expression of caspase-11 triggered by P. brasiliensis infection of macrophages depends on IFN-β production, because its inhibition reduced procaspase-11 levels. Curiously, caspase-11 deficiency did not impair IL-1β production, however caspase-11 was required for a rapid pore-mediated cell lysis. The plasma membrane rupture facilitated the release of IL-1α, which was necessary to induce NO production and restrict fungal replication. Furthermore, P. brasiliensis-infected macrophages required IL-1α to produce optimal levels of IL-6, a major component of Th17 lymphocyte differentiation. Indeed, IL-1α deficiency accounted for a significant reduction of Th17 lymphocytes in lungs of infected mice, correlating with diminished neutrophil infiltration in the lungs. Strikingly, we identified that IL-1α directly reprograms the transcriptional profile of Th17-committed lymphocytes, increasing cellular proliferation, as for boosting IL-17 production by these cells. Beyond neutrophil chemotaxis in vivo, IL-17 also amplified IL-1α production by infected macrophages in vitro, endorsing a critical amplification loop of the inflammatory response. Therefore, our data suggest that the IFN-β/caspase-11/IL-1α pathway shapes a protective antifungal Th17 immunity, revealing a molecular mechanism underlying the cross-talk between innate and adaptive immunity. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/31425553/Caspase-11-dependent_IL-1α_release_boosts_Th17_immunity_against_Paracoccidioides_brasiliensis L2 - http://dx.plos.org/10.1371/journal.ppat.1007990 DB - PRIME DP - Unbound Medicine ER -