PMC:4928686 / 9868-11341 JSONTXT

{"project":"2_test","denotations":[{"id":"25788396-25440119-121220486","span":{"begin":773,"end":774},"obj":"25440119"},{"id":"25788396-25440119-121220486","span":{"begin":773,"end":774},"obj":"25440119"},{"id":"25788396-19210221-121220487","span":{"begin":906,"end":908},"obj":"19210221"},{"id":"25788396-19210221-121220487","span":{"begin":906,"end":908},"obj":"19210221"},{"id":"25788396-16521279-121220488","span":{"begin":905,"end":907},"obj":"16521279"},{"id":"25788396-16521279-121220488","span":{"begin":905,"end":907},"obj":"16521279"},{"id":"25788396-12093008-68933167","span":{"begin":363,"end":365},"obj":"12093008"},{"id":"25788396-12093008-68933167","span":{"begin":363,"end":365},"obj":"12093008"},{"id":"25788396-25440119-68933168","span":{"begin":773,"end":774},"obj":"25440119"},{"id":"25788396-25440119-68933168","span":{"begin":773,"end":774},"obj":"25440119"},{"id":"25788396-16521279-68933169","span":{"begin":902,"end":904},"obj":"16521279"},{"id":"25788396-16521279-68933169","span":{"begin":902,"end":904},"obj":"16521279"},{"id":"25788396-19210221-68933170","span":{"begin":906,"end":908},"obj":"19210221"},{"id":"25788396-19210221-68933170","span":{"begin":906,"end":908},"obj":"19210221"}],"text":"One major difference between humans and murine models that has gone overlooked is the immune experience of subjects in sepsis studies. Welsh and Selin first popularized the idea that previous immune responses to infectious challenges might shape and influence subsequent responses to new antigens, a concept that they termed “heterologous immunity” (reviewed in [47]). Most adult humans have been exposed to multiple previous virus infections, not to mention a standard battery of immunizations that may have significant and long-lasting impact on their immune responses to sepsis. For example, 60 % of patients have been infected by CMV prior to onset of critical illness, and the prevalence of other herpes family viruses is also very high during adulthood (reviewed in [3]). As previously discussed, precedent herpesvirus infection has the potential to significantly alter host responses to sepsis [34, 48]. Thus, comparing “immune-experienced” human immune responses that have been manipulated by innumerable previous infectious encounters to relatively “immune naïve” immune responses in mice is likely a comparison between the figurative apple and orange. Given the myriad combinations of precedent antigen experience, including the number, type, sequence, organism load and of course timing of exposure (recent versus remote), it may be required for murine models of sepsis to include such immune preconditioning to adequately recapitulate human responses to sepsis."}