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. 2025 Dec;16(1):2440554.
doi: 10.1080/21505594.2024.2440554. Epub 2024 Dec 28.

Human macrophage response to the emerging enteric pathogen Aeromonas veronii: Inflammation, apoptosis, and downregulation of histones

Nicholas Naidovski  1 , Sarah K T Chong  1 , Fang Liu  1 , Stephen M Riordan  2 , Michael C Wehrhahn  3 , Christopher Yuwono  1 , Li Zhang  1
Affiliations

Human macrophage response to the emerging enteric pathogen Aeromonas veronii: Inflammation, apoptosis, and downregulation of histones

Nicholas Naidovski et al. Virulence. 2025 Dec.

Abstract

This study investigated the pathogenic mechanisms of Aeromonas veronii in macrophages. THP-1 derived macrophages were used as a human macrophage model and were treated with A. veronii strain AS1 isolated from intestinal biopsies of an IBD patient, or Escherichia coli strain K-12. RNA was extracted and subjected to RNA sequencing and comparative transcriptomic analyses. Protein levels of IL-8, IL-1β, IL-18, and TNFα were measured using ELISA, and apoptosis was assessed using caspase 3/7 assays. Both A. veronii AS1 and E. coli K-12 significantly upregulated the expression of many genes involving inflammation. At the protein level, A. veronii AS1 induced significantly higher levels of IL-8, TNFα, mature IL-18 and IL-1β than E. coli K-12, and led to greater elevation of caspase 3/7 activities. Both A. veronii AS1 and E. coli K-12 upregulated the expression of CASP5, but not other caspase genes. A. veronii AS1 significantly downregulated the expression of 20 genes encoding histone proteins that E. coli K-12 did not. The more profound pathogenic effects of A. veronii in inducing inflammation and apoptosis in macrophages than E. coli K-12 are consistent with its role as a human enteric pathogen. The upregulated expression of CASP5 and increased release of IL-1β and IL-18 support the role of CASP5 in activation of non-canonical inflammasome. The downregulation of histone genes by A. veronii suggests a unique impact on host cell gene expression, which may represent a novel virulence strategy. These findings advance the understanding of pathogenic mechanisms of the emerging human enteric pathogen A. veronii.

Keywords: Aeromonas; Aeromonas veronii; Escherichia coli; THP-1 macrophages; gastroenteritis; macrophages.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
A. veronii AS1 and E. coli K12 upregulated and downregulated expression of genes in THP-1 macrophages.
Figure 2.
Figure 2.
A. veronii AS1 induced the downregulation of histone encoding genes on chromosome 6.
Figure 3.
Figure 3.
The impact of A. veronii AS1 or E. coli K-12 on biological processes in THP-1 macrophages.
Figure 4.
Figure 4.
Morphology and viability of THP-1 macrophages following treatment with A. veronii AS1 or E. coli K-12.
Figure 5.
Figure 5.
Production of IL-8 and TNFα in THP-1 macrophages induced by A. veronii AS1 or E. coli K-12 treatment.
Figure 6.
Figure 6.
Production of IL-1β and IL-18 in THP-1 macrophages induced by A. veronii AS1 or E. coli K-12 treatment.
Figure 7.
Figure 7.
Caspase 3/7 activity induced by A. veronii AS1 or E. coli K-12 treatment of THP-1 macrophages.
Figure 8.
Figure 8.
Summary of the pathogenic effects and mechanisms induced by A. veronii bacterial treatment of human macrophages.
See this image and copyright information in PMC

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