Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.

Autor: Hirako IC; Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Lazare Research Building, 3rd Floor, Worcester, MA, USA., Antunes MM; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Rezende RM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Hojo-Souza NS; Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil., Figueiredo MM; Universidade Estadual de Minas Gerais, Divinópolis, MG, Brazil., Dias T; Escola de Ciências Farmacêuticas - Universidade de São Paulo, São Paulo, SP, Brazil., Nakaya H; Escola de Ciências Farmacêuticas - Universidade de São Paulo, São Paulo, SP, Brazil., Menezes GB; Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Gazzinelli RT; Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil. ricardo.gazzinelli@umassmed.edu.; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Lazare Research Building, 3rd Floor, Worcester, MA, USA. ricardo.gazzinelli@umassmed.edu.; Departamento de Bioquímica E Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. ricardo.gazzinelli@umassmed.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Nov 17; Vol. 12 (1), pp. 19805. Date of Electronic Publication: 2022 Nov 17.
DOI: 10.1038/s41598-022-23858-7
Abstrakt: Kupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections. Similar to patients, infection with Plasmodium chabaudi induced acute liver damage as determined by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. This was associated with accumulation of hemozoin, increased of proinflammatory response and impaired bacterial and viral clearance, which led to pathogen spread to other organs. In line with this, mice infected with Plasmodium had enhanced mortality during secondary infections, which was associated with increased production of mitochondrial superoxide, lipid peroxidation and increased free iron within KCs-hallmarks of cell death by ferroptosis. Therefore, we revealed that accumulation of iron with KCs, triggered by uptake of circulating hemozoin, is a novel mechanism of macrophage depletion and liver inflammation during malaria, providing novel insights on host susceptibility to secondary infections. Malaria can cause severe liver damage, along with depletion of liver macrophages, which can predispose individuals to secondary infections and enhance the chances of death.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje