Preservation of the Innate Immune Response toClostridioides difficileInfection in Hospitalized Immunocompromised Patients

Abstract

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 (G-CSF, IL-10, IL-15, IL-1β, IL-4, IL-6, IL-8, and TNF-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASC) (NAAT positive, without diarrhea) with and without immunocompromise. Results 123 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 <0.05). In stool, IL-1β and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P <0.05). Stool concentrations of IL-1β demonstrated significant differences between the groups (median: ICHs 10.97 pg/mL, non-ICH: 9.71 pg/mL and ASC 0.56 pg/mL) (P<0.0001). 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.

Novel insights into phage biology of the pathogenClostridioides difficilebased on the active virome

“…The personal health condition significantly affects resistance against a C. difficile infection, but the infecting strain is of relevance as well (6). Different C. difficile strains are linked to divergent virulence, and various aspects such as toxin production levels or secondary bile salt resistance were shown to correlate with disease severity (7,8). However, these studies also partially contradict in the concluded relevance of specific features on virulence.…”