Activation and survival of neutrophils induced by ArtinM: signaling pathways and m...
| Full text | |
| Author(s): |
Ketelut-Carneiro, Natalia
[1]
;
Silva Souza, Camila Oliveira
[1]
;
Benevides, Luciana
[1]
;
Gardinassi, Luiz Gustavo
[2]
;
Silva, Maria Claudia
[1]
;
Tavares, Lucas Alves
[3]
;
Zamboni, Dario Simoes
[3]
;
Silva, Joao Santana
[1, 4]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Analyses Toxicol & Food Sci, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell Biol, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, FIOCRUZ, Biinst Translat Med Project, Ribeirao Preto, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | PLOS PATHOGENS; v. 15, n. 8 AUG 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
The granulomatous lesion resulting from infection with the fungus Paracoccidioides brasiliensis is characterized by a compact aggregate of mature cells, surrounded by a fibroblastand 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-1 alpha and IL-1 beta. In this study, we addressed the mechanisms underlying IL-1 alpha 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-beta production, because its inhibition reduced procaspase11 levels. Curiously, caspase-11 deficiency did not impair IL-1 beta production, however caspase-11 was required for a rapid pore-mediated cell lysis. The plasma membrane rupture facilitated the release of IL-1 alpha, which was necessary to induce NO production and restrict fungal replication. Furthermore, P. brasiliensis-infected macrophages required IL-1 alpha to produce optimal levels of IL-6, a major component of Th17 lymphocyte differentiation. Indeed, IL-1 alpha 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-1 alpha 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-1 alpha production by infected macrophages in vitro, endorsing a critical amplification loop of the inflammatory response. Therefore, our data suggest that the IFN-beta/caspase-11/IL-1 alpha pathway shapes a protective antifungal Th17 immunity, revealing a molecular mechanism underlying the cross-talk between innate and adaptive immunity. (AU) | |
| FAPESP's process: | 13/21295-9 - Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis |
| Grantee: | Natália Ketelut Carneiro |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| 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: | 12/14524-9 - Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria |
| Grantee: | João Santana da Silva |
| Support type: | Research Projects - Thematic Grants |