Summary
Our prior publication detailing how sepsis influences subsequent development of EAE presented a conceptual advance in understanding the post-sepsis chronic immunoparalysis state (Jensen et al., 2020). However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. Herein, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis incidence among MS, relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis well-established murine models of MS and sepsis, EAE and CLP, respectively, were utilized. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and S. pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* Co-first authors: Isaac J. Jensen and Samantha N. Jensen
Funding: Authors are supported by grants from the National institutes of Health: 5R01AI114543, 1R35GM134880 to VPB, R01GM115462, 1R35GM140881 to TSG, 5R01AI137075 to AKM, T32AI007511, T32AI007485 to IJJ, T32AI007485, and 1R01AI137075-S1 to SNJ; Veterans Health Administration: I01BX001324 to TSG; University of Iowa Environmental Health Sciences Research Center, NIEHS/NIH: P30 ES005605 to AKM