Human neutrophils are resistant to Clostridioides difficile toxin B

Abstract

Objective: The main objective of this study was to evaluate the glucosyltransferase activity of C. difficile TcdB on the activity of human PMNs.

Methods: To better understand the interaction between PMNs and TcdB, PMNs were treated with sub-lethal concentrations of TcdB. We evaluated: (i) the glucosylation of GTPases, (ii) the phagocytic and bactericidal activity, and (iii) PMNs activation (through quantification of TNF-α, IL-8, and expression of CD11b cell surface activation marker).

Results: We found that TcdB did not glucosylate RhoA and Rac1 GTPases and did not affect the phagocytic or bactericidal capacity of PMNs. Moreover, TcdB did not increase the production of TNF-α, IL-8, or the expression of activation marker CD11b. The only significant effect of TcdB on PMNs was the partial inhibition of TNF-α and IL-8 production and the diminished expression of CD11b induced by E. coli-LPS.

Conclusion: Our results show that human PMNs are resistant to TcdB GTPase glucosyltransferase activity against RhoA and Rac1.

Keywords: Clostridioides difficile; Glucosylation; Neutrophils; TcdB.