Susceptibility to Infections During Acute Liver Injury Depends on Transient Disruption of Liver Macrophage Niche

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dc.creatorMateus Eustáquio Lopes
dc.creatorGustavo Batista Menezes
dc.creatorBrenda Naemi Nakagaki
dc.creatorMatheus Silvério Mattos
dc.creatorGabriel Henrique Campolina-Silva
dc.creatorRaquel de Oliveira Meira
dc.creatorPierre Henrique de Menezes Paixao
dc.creatorAndré gustavo Oliveira
dc.creatorLucas D. Faustino
dc.creatorRicardo Gonçalves
dc.date.accessioned2023-11-16T21:22:21Z
dc.date.accessioned2025-09-09T00:51:49Z
dc.date.available2023-11-16T21:22:21Z
dc.date.issued2022-07-28
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.3389/fimmu.2022.892114
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/1843/61017
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofFrontiers in Immunology
dc.rightsAcesso Aberto
dc.subjectMacrófagos
dc.subjectCélulas de Kupffer
dc.subjectFígado
dc.subjectInflamação
dc.subjectTerapia Baseada em Transplante de Células e Tecidos
dc.subjectInfecções
dc.subject.otherKupffer cell
dc.subject.otherMacrophage niche
dc.subject.otherAcute liver injury
dc.subject.otherInflammation
dc.subject.otherCell therapy
dc.subject.otherSystemic infection
dc.titleSusceptibility to Infections During Acute Liver Injury Depends on Transient Disruption of Liver Macrophage Niche
dc.typeArtigo de periódico
local.citation.epage18
local.citation.spage892114
local.citation.volume13
local.description.resumoKupffer cells are the primary liver resident immune cell responsible for the liver firewall function, including clearance of bacterial infection from the circulation, as they are strategically positioned inside the liver sinusoid with intimate contact with the blood. Disruption in the tissue-resident macrophage niche, such as in Kupffer cells, can lead to a window of susceptibility to systemic infections, which represents a significant cause of mortality in patients with acetaminophen (APAP) overdose-induced acute liver injury (ALI). However, how Kupffer cell niche disruption increases susceptibility to systemic infections in ALI is not fully understood. Using a mouse model of ALI induced by APAP overdose, we found that Kupffer cells upregulated the apoptotic cell death program and were markedly reduced in the necrotic areas during the early stages of ALI, opening the niche for the infiltration of neutrophils and monocyte subsets. In addition, during the resolution phase of ALI, the remaining tissue macrophages with a Kupffer cell morphology were observed forming replicating cell clusters closer to necrotic areas devoid of Kupffer cells. Interestingly, mice with APAP-induced liver injury were still susceptible to infections despite the dual cellular input of circulating monocytes and proliferation of remaining Kupffer cells in the damaged liver. Therapy with bone marrow-derived macrophages (BMDM) was shown to be effective in occupying the niche devoid of Kupffer cells following APAP-induced ALI. The rapid BMDM migration to the liver and their positioning within necrotic areas enhanced the healing of the tissue and restored the liver firewall function after BMDM therapy. Therefore, we showed that disruption in the Kupffer cell niche and its impaired function during acute liver injury are key factors for the susceptibility to systemic bacterial infections. In addition, modulation of the liver macrophage niche was shown to be a promising therapeutic strategy for liver injuries that reduce the Kupffer cell number and compromise the organ function.
local.identifier.orcidhttps://orcid.org/0000-0002-1127-4483
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE PATOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://www.frontiersin.org/articles/10.3389/fimmu.2022.892114/full

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