Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Background: Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods: We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results: One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1ß and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1ß demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions: In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.