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. 2020 Dec:66:102275.
doi: 10.1016/j.anaerobe.2020.102275. Epub 2020 Sep 22.

Type 2 cytokines IL-4 and IL-5 reduce severe outcomes from Clostridiodes difficile infection

Alexandra N Donlan  1 , Morgan E Simpson  2 , William A Petri Jr  3
Affiliations

Type 2 cytokines IL-4 and IL-5 reduce severe outcomes from Clostridiodes difficile infection

Alexandra N Donlan et al. Anaerobe. 2020 Dec.

Abstract

Clostridiodes difficile infection (CDI) is the leading cause of hospital-acquired gastrointestinal infections in the U.S. While the immune response to C. difficile is not well understood, it has been shown that severe disease is accompanied by high levels of infiltrating immune cells and pro-inflammatory cytokine production. This study tests the roles of two type 2 cytokines, IL-4 and IL-5, in mediating protection in a murine model of disease. Administration of IL-5 protected from mortality due to CDI, and both IL-4 and IL-5 were protective against severe disease symptoms. Together, the results from this study increase our understanding of how type 2 immune signaling processes are protective from severe C. difficile infection.

Keywords: C. difficile; Cytokines; Type 2 immunity.

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Conflict of interest statement

Declaration of competing interest WP is a consultant for TechLab, Inc. AD has Provision Patent for the use of Anti-IL-13Ra2 for the Treatment of C. difficile.

Figures

Figure 1.
Figure 1.. IL-5 protects from severe C. difficile infection and alters the immune compartment.
(A) Mice were administered antibiotics in their drinking water for three days, followed by two days of clean water and one i.p. injection of Clindamycin before challenge with 104 spores of C. difficile strain R20291 and i.p. injection of 5 μg rIL-5 or PBS control. Compared to control, mice treated with rIL-5 had (B) lower clinical scores, which are indicative of disease severity, and (C) reduced mortality by three days post-infection (DPI). (D) Mice treated with IL-5 did not have any change in weight loss compared for control. (E) Flow cytometry on colonic lamina propria cells was run on day 2 of infection. IL-5 treatment resulted in slightly lowered total CD45+ cells (p = .06), and significant reductions in neutrophils (CD11B+Ly6G+Ly6C-) (p = .02). (F) IL-5 treatment resulted in decreased proportion of neutrophils (p = .018) and an increased proportion of eosinophils (CD11B+Siglec-F+) (p = .027) as a percentage of CD11B+ myeloid cells. N= 10 mice/group. Values shown with (*) are statistically (p<.05) different using a Student’s t-test.
Figure 2.
Figure 2.. IL-4 protects from disease by enhancing recovery.
Administration of IL-4 on days 1-, 4, and 1 (A), resulted in more rapidly recovered weight loss starting on day 3 of infection, compared to the PBS control group which began recovery on day 4 (B). (C) IL-4 treatment also resulted in decreased clinical scores on day 3.5 and 4. (D) Mortality between the two groups was not changed by IL-4 treatment. N= 10 mice/group. Values shown with (*) are statistically (p<.05) different using a Student’s t-test.
See this image and copyright information in PMC

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