| Full text | |
| Author(s): |
de Araujo, Eliseu F.
[1]
;
Loures, Flavio V.
[1]
;
Preite, Nycolas W.
[1]
;
Feriotti, Claudia
[1]
;
Galdino, Nayane A. L.
[1]
;
Costa, Tania A.
[1]
;
Calich, Vera L. G.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | FRONTIERS IN IMMUNOLOGY; v. 12, APR 16 2021. |
| Web of Science Citations: | 1 |
| Abstract | |
In agreement with other fungal infections, immunoprotection in pulmonary paracoccidioidomycosis (PCM) is mediated by Th1/Th17 cells whereas disease progression by prevalent Th2/Th9 immunity. Treg cells play a dual role, suppressing immunity but also controlling excessive tissue inflammation. Our recent studies have demonstrated that the enzyme indoleamine 2,3 dioxygenase (IDO) and the transcription factor aryl hydrocarbon receptor (AhR) play an important role in the immunoregulation of PCM. To further evaluate the immunomodulatory activity of AhR in this fungal infection, Paracoccidioides brasiliensis infected mice were treated with two different AhR agonists, L-Kynurenin (L-Kyn) or 6-formylindole {[}3,2-b] carbazole (FICZ), and one AhR specific antagonist (CH223191). The disease severity and immune response of treated and untreated mice were assessed 96 hours and 2 weeks after infection. Some similar effects on host response were shared by FICZ and L-Kyn, such as the reduced fungal loads, decreased numbers of CD11c+ lung myeloid cells expressing activation markers (IA, CD40, CD80, CD86), and early increased expression of IDO and AhR. In contrast, the AhR antagonist CH223191 induced increased fungal loads, increased number of pulmonary CD11c+ leukocytes expressing activation markers, and a reduction in AhR and IDO production. While FICZ treatment promoted large increases in ILC3, L-Kyn and CH223191 significantly reduced this cell population. Each of these AhR ligands induced a characteristic adaptive immunity. The large expansion of FICZ-induced myeloid, lymphoid, and plasmacytoid dendritic cells (DCs) led to the increased expansion of all CD4+ T cell subpopulations (Th1, Th2, Th17, Th22, and Treg), but with a clear predominance of Th17 and Th22 subsets. On the other hand, L-Kyn, that preferentially activated plasmacytoid DCs, reduced Th1/Th22 development but caused a robust expansion of Treg cells. The AhR antagonist CH223191 induced a preferential expansion of myeloid DCs, reduced the number of Th1, Th22, and Treg cells, but increased Th17 differentiation. In conclusion, the present study showed that the pathogen loads and the immune response in pulmonary PCM can be modulated by AhR ligands. However, further studies are needed to define the possible use of these compounds as adjuvant therapy for this fungal infection. (AU) | |
| FAPESP's process: | 18/14762-3 - Immunosuppression in paracoccidioidomycosis: the regulatory role of myeloid-derived suppressor cells (MDSCs) on host immunity, tissue pathology and genetic adaptation of fungal cells |
| Grantee: | Flávio Vieira Loures |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 16/23189-0 - Modulation of Treg/Th17 responses by Aryl Hydrocarbon Receptor Ligands in the Search for an Immunotherapeutic Procedure for Pulmonary Paracoccidioidomycosis |
| Grantee: | Vera Lucia Garcia Calich |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 11/51258-2 - Influence of the enzyme indoleamine-2,3-dioxygenase (IDO) in the differentiation and function of dendritic cells and regulatory T cells in the pulmonary paracoccidioidomycosis of resistant and susceptible mice to P. brasiliensis infection |
| Grantee: | Vera Lucia Garcia Calich |
| Support Opportunities: | Regular Research Grants |