Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis

Front Cell Infect Microbiol. 2023 Nov 16:13:1275954. doi: 10.3389/fcimb.2023.1275954. eCollection 2023.

Abstract

Paracoccidioides spp. is the etiologic agent of Paracoccidioidomycosis (PCM), a systemic disease with wide distribution in Latin America. Macrophages are very important cells during the response to infection by P. brasiliensis. In this study, we performed a proteomic analysis to evaluate the consequences of P. brasiliensis yeast cells on the human THP-1 macrophage proteome. We have identified 443 and 2247 upregulated or downregulated proteins, respectively, in macrophages co-cultured with yeast cells of P. brasiliensis in comparison to control macrophages unexposed to the fungus. Proteomic analysis revealed that interaction with P. brasiliensis caused metabolic changes in macrophages that drastically affected energy production pathways. In addition, these macrophages presented regulated many factors related to epigenetic modifications and gene transcription as well as a decrease of many proteins associated to the immune system activity. This is the first human macrophage proteome derived from interactions with P. brasiliensis, which contributes to elucidating the changes that occur during the host response to this fungus. Furthermore, it highlights proteins that may be targets for the development of new therapeutic approaches to PCM.

Keywords: Paracoccidioides brasiliensis; immunometabolism; macrophages; metabolic reprogramming; proteomic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Macrophages / microbiology
  • Paracoccidioides*
  • Proteome / metabolism
  • Proteomics
  • Saccharomyces cerevisiae

Substances

  • Proteome

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was done at Universidade Federal de Goiás with financial support of Fundação de Apoio a Pesquisa de Goiás (FAPEG) and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES)/Ministry of Education, Brazil-Finance Code 001.; AF is a fellow of CAPES; FR-D and CS are fellow researchers of National Council for Scientific and Technological Development (CNPq), Brazil; FR-D and CS are members of National Institute of Science and Technology of the strategies in host-pathogen interaction (INCT-IPH), supported by FAPEG (grant n. 465771/2014-9), Brazil.