Efficient cell model for assessing inflammatory responsive genes in Mycobacterium tuberculosis and SARS-CoV-2 co-infection

Tuberculosis (Edinb). 2025 Sep:154:102672. doi: 10.1016/j.tube.2025.102672. Epub 2025 Jul 1.

Abstract

Mycobacterium tuberculosis (Mtb) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may induce immunopathology with extensive lung damage in hosts. To elucidate the dynamics of co-infection Mtb and SARS-CoV-2 and its impact on inflammatory mediators' expression, we conducted a study to evaluate A549, lung epithelial cells, as a potential model for hosting both pathogens simultaneously. Cell infection initiated with Mtb H37Rv and following a 24-h incubation period, the cells were then infected with SARS-CoV-2. After a 72 h incubation period, a precision test was conducted for both pathogens, and total RNA was extracted for subsequent analysis of gene expression by RT-qPCR of the target genes: IFN-γ, TNF-α, IL-6, and IL-1β. Additionally, the levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α in the culture supernatants were measured. A549 cells are a stable and reliable cellular model for co-infection between Mycobacterium tuberculosis and SARS-CoV-2. Co-infection with both pathogens led to downregulation of IFN-γ, TNF-α, and IL-10, and upregulation of IL-6 and IL-1β compared to uninfected cells. A549 cells function as a cellular model for co-infection and seems a good model for elucidating host inflammatory responses in the initial site of infection.

Keywords: COVID-19; Host; Pathogens; Tuberculosis.

MeSH terms

  • A549 Cells
  • COVID-19* / genetics
  • COVID-19* / immunology
  • COVID-19* / virology
  • Coinfection*
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators* / metabolism
  • Mycobacterium tuberculosis* / genetics
  • Mycobacterium tuberculosis* / immunology
  • Mycobacterium tuberculosis* / pathogenicity
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / pathogenicity

Substances

  • Cytokines
  • Inflammation Mediators