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CARD9 mutations and T cell immune response in patients with chromoblastomycosis

Tatiana Sobianski Herman1,2, Conceição de M. Pedrozo e S. Azevedo3, Anamelia Lorenzetti Bocca4, Bruna Jacomel Favoreto de Souza Lima1,5,11, Caroline Pavini Beato-Souza6, Emanuel Razzolini7,11, Sirlei G. Marques12, Natália Nunes3, Bruno Paulo Rodrigues Lustosa7,11, Daniel Wagner Castro Lima Santos8,9, Flávio Queiroz-Telles10, Sybren de Hoog1,5, Renata R. Gomes1,6,11# and Vania Aparecida Vicente1,6,7,11#

1Microbiology, Parasitology and Pathology Graduate Program, Department of Pathology, Federal University of Paraná, Curitiba, Brazil; 2Graduate Program in Molecular Pathology, University of Brasilia, Brasilia, Brazil; 3 Department of Medicine I, Graduate Program in Health Science, Federal University of Maranhão, São Luis, Brazil; 4Applied Immunology Laboratory, Cell Biology Department, Institute of Biological Science, University of Brasília, Brasilia, Brazil; 5Department of Medical Microbiology, Radboudumc/CWZ Center of Expertise in Mycology, Nijmegen, The Netherlands; 6Department of Pathology, Federal University of Paraná, Curitiba, Brazil; 7Engineering Bioprocess and Biotechnology Graduate Program, Department of Bioprocess Engineering and Biotechnology, Federal University of Paraná, Curitiba, Brazil; 8Change to d’Or Institute of Research and Education; 9Clinical Hospital of Federal University of Maranhão; 10Department of Public Health, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil; 11Microbiological Collections of Paraná Network, Curitiba, Brazil; 12Clinical Hospital of Federal University of Maranhão Presidente Dutra, São Luís, Brazil 

Abstract

Background. CARD9 is an adaptive protein in myeloid cellsthat is important in the immune response to intracellularfungi and bacteria. It is present in the intracellular cascade ofantigen-antigen-presenting cells that perform the recognitionof fungal antigens by C-type lectin receptor recognitionmolecules. Mutations in this gene have been associatedwith defects in the polarization of T cells, increasing thesusceptibility and severity of the conditions in fungalinfections. The immune response in chromoblastomycosis(CBM) is still not completely elucidated.
Objectives. The main objective of this work was to identifymutations in CARD9 associated with changes of immuneresponse in patients with CBM.
Methods
. Sequencing of the 12 exons of the CARD9 geneof 23 patients with CBM was carried out. For the surveyof clinical data, the criterion for classification of lesionsand the severity of the condition was adopted, consideringthe number, extent, and dissemination of lesions as mild,moderate, or severe. TNF-α, IL-6 and IL-10 were measuredprior to treatment.
Results
. A correlation was found between severity of thecondition presented by the patients and the presence of themutation (p<0.05). Besides, low levels of IL-6 and TNF-α were observed in severe cases, both related to the Th1 and Th17 profile. However, no significant statistic association could be established between the polarization of the immune response and the presence of the mutation (p>0.08).
Conclusions
. The mutation has a significantly increasedpresence in the studied CBM patient cohort compared toits known prevalence in the healthy population. There wasan association between severity of the condition presentedby the patients and the presence of the mutation. Anassociation between polarization of the immune responseand severity was observed, however a larger populationshould be analyzed for statistical significance. Patients withCBM previously were thought to be immunocompetent, butour data indicate that inherited immune disorders may play arole in the development of the disease. 

Open Access

Cite this article :
Sobianski Herman T, Azevedo CMPS, Bocca AL, Lima JFS, Beato-Souza CP, Razzolini E, Marques SG, Nunes N, Rodrigues Lustosa BP, Santos DWCL, Queiroz-Telles F, de Hoog S, Gomes RR, Vicente VA. 2024. CARD9 mutations and T cell immune response in patients with
chromoblastomycosis. One Health Mycology 1(1), 14-23.

ISSN nummer: xxxxxx

Keywords: chromoblastomycosis; black yeast; CARD9; Fonsecaea; phaeohyphomycosis; inherited immune disorder

Article highlights:

  • Presence of mutation in CARD9 is associated with moderate and
    severe lesions in patients with chromoblastomycosis (CBM).
  • Low levels of IL-6 and TNF-α were observed in severe cases.

#Correspondence:vaniava63@gmail.com, rrgrenata@gmail.com

Article info:
Received 8 December 2023
Revised 25 January 2024
Accepted 29 January 2024
Appeared online 10 February 2024
One Health Mycology 1(1): 14−23, 2024