Immune response resetting in ongoing sepsis

Página do item simplificado
dc.contributor.authorNowill A.E.
dc.contributor.authorFornazin M.C.
dc.contributor.authorSpago M.C.
dc.contributor.authorNeto V.D.
dc.contributor.authorPinheiro V.R.P.
dc.contributor.authorAlexandre S.S.S.
dc.contributor.authorMoraes E.O.
dc.contributor.authorSouza G.H.M.F.
dc.contributor.authorEberlin M.N.
dc.contributor.authorMarques L.A.
dc.contributor.authorMeurer E.C.
dc.contributor.authorFranchi G.C.
dc.contributor.authorDe Campos-Lima P.O.
dc.date.accessioned2024-03-12T23:52:09Z
dc.date.available2024-03-12T23:52:09Z
dc.date.issued2019
dc.description.abstract© 2019 by The American Association of Immunologists, Inc.Cure of severe infections, sepsis, and septic shock with antimicrobial drugs is a challenge because morbidity and mortality in these conditions are essentially caused by improper immune response.We have tested the hypothesis that repeated reactivation of established memory to pathogens may reset unfavorable immune responses. We have chosen for this purpose a highly stringent mouse model of polymicrobial sepsis by cecum ligation and puncture. Five weeks after priming with a diverse Ag pool, high-grade sepsis was induced in C57BL/6j mice that was lethal in 24 h if left untreated. Antimicrobial drug (imipenem) alone rescued 9.7% of the animals from death, but >5-fold higher cure rate could be achieved by combining imipenem and two rechallenges with the Ag pool (p < 0.0001). Antigenic stimulation fine-tuned the immune response in sepsis by contracting the total CD3+ T cell compartment in the spleen and disengaging the hyperactivation state in the memory T subsets, most notably CD8+ T cells, while preserving the recovery of naive subsets. Quantitative proteomics/lipidomics analyses revealed that the combined treatment reverted the molecular signature of sepsis for cytokine storm, and deregulated inflammatory reaction and proapoptotic environment, as well as the lysophosphatidylcholine/phosphatidylcholine ratio. Our results showed the feasibility of resetting uncontrolled hyperinflammatory reactions into ordered hypoinflammatory responses by memory reactivation, thereby reducing morbidity and mortality in antibiotic-treated sepsis. This beneficial effect was not dependent on the generation of a pathogen-driven immune response itself but rather on the reactivation of memory to a diverse Ag pool that modulates the ongoing response.
dc.description.firstpage1298
dc.description.issuenumber5
dc.description.lastpage1312
dc.description.volume203
dc.identifier.doi10.4049/jimmunol.1900104
dc.identifier.issn1550-6606
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/35213
dc.relation.ispartofJournal of Immunology
dc.rightsAcesso Aberto
dc.titleImmune response resetting in ongoing sepsis
dc.typeArtigo
local.scopus.citations19
local.scopus.eid2-s2.0-85071708233
local.scopus.subjectAnimals
local.scopus.subjectApoptosis
local.scopus.subjectCD3 Complex
local.scopus.subjectCD8-Positive T-Lymphocytes
local.scopus.subjectCecum
local.scopus.subjectCytokines
local.scopus.subjectDisease Models, Animal
local.scopus.subjectFemale
local.scopus.subjectImmunologic Memory
local.scopus.subjectInflammation
local.scopus.subjectLipidomics
local.scopus.subjectLysophosphatidylcholines
local.scopus.subjectMice
local.scopus.subjectMice, Inbred C57BL
local.scopus.subjectPhosphatidylcholines
local.scopus.subjectProteomics
local.scopus.subjectSepsis
local.scopus.subjectShock, Septic
local.scopus.subjectSpleen
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071708233&origin=inward
Arquivos
Coleções
Artigos de periódico