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. 2024 Jan-Dec;16(1):2399215.
doi: 10.1080/19490976.2024.2399215. Epub 2024 Sep 16.

Enterotoxigenic Escherichia coli heat labile enterotoxin affects neutrophil effector functions via cAMP/PKA/ERK signaling

Jinglin Ma  1 , Leen Hermans  1 , Matthias Dierick  1 , Hans Van der Weken  1 , Eric Cox  1 , Bert Devriendt  1
Affiliations

Enterotoxigenic Escherichia coli heat labile enterotoxin affects neutrophil effector functions via cAMP/PKA/ERK signaling

Jinglin Ma et al. Gut Microbes. 2024 Jan-Dec.

Abstract

Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal illness in humans and animals, induced by enterotoxins produced by these pathogens. Despite the crucial role of neutrophils in combatting bacterial infections, our understanding of how enterotoxins impact neutrophil function is limited. To address this knowledge gap, we used heat-labile enterotoxin (LT) and heat-stable enterotoxin a (STa) to investigate their impact on the effector functions of neutrophils. Our study reveals that pSTa does not exert any discernible effect on the function of neutrophils. In contrast, LT altered the migration and phagocytosis of neutrophils and induced the production of inflammatory factors via activation of cAMP/PKA and ERK1/2 signaling. LT also attenuated the release of neutrophil extracellular traps by neutrophils via the PKA signaling pathway. Our findings provide novel insights into the impact of LT on neutrophil function, shedding light on the underlying mechanisms that govern its immunoregulatory effects. This might help ETEC in subverting the immune system and establishing infection.

Keywords: ETEC; Heat labile enterotoxin; cAMP/PKA/ERK signaling; neutrophils; pig.

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Conflict of interest statement

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

Figures

Figure 1.
Figure 1.
LT binds to neutrophils and triggers their migration.
Figure 2.
Figure 2.
LT, but not pSta, decreases the phagocytosis ability of neutrophils.
Figure 3.
Figure 3.
LT downregulated CD11b cell surface expression of neutrophils.
Figure 4.
Figure 4.
Neutrophils respond to LT by increased production of pro-inflammatory cytokines and chemokines.
Figure 5.
Figure 5.
LT promoted neutrophils to generate NETs in vitro.
Figure 6.
Figure 6.
LT induced activation of the cAMP/PKA signaling pathway in porcine neutrophils.
Figure 7.
Figure 7.
LT induced ERK1/2 phosphorylation in neutrophils.
Figure 8.
Figure 8.
Inhibition of PKA and ERK1/2 affected migration and inflammatory factor production induced by LT.
Figure 9.
Figure 9.
Graphical summary of the results. The full lines indicate direct effects, while the dashed lines indicate indirect effects of LT on neutrophils.
See this image and copyright information in PMC

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