title: Autophagy is redundant for the host defense against systemic Candida albicans infections.
abstract: Autophagy has been demonstrated to play an important role in the immunity against intracellular pathogens, but very little is known about its role in the host defense against fungal pathogens such as Candida albicans. Therefore, the role of autophagy for the host defense against C. albicans was assessed by complementary approaches using mice defective in autophagy, as well as immunological and genetic studies in humans. Although C. albicans induced LC3-II formation in macrophages, myeloid cell-specific ATG7(-/-) mice with defects in autophagy did not display an increased susceptibility to disseminated candidiasis. In in vitro experiments in human blood mononuclear cells, blocking autophagy modulated cytokine production induced by lipopolysaccharide, but not by C. albicans. Furthermore, autophagy modulation in human monocytes did not influence the phagocytosis and killing of C. albicans. Finally, 18 single-nucleotide polymorphisms in 13 autophagy genes were not associated with susceptibility to candidemia or clinical outcome of disease in a large cohort of patients, and there was no correlation between these genetic variants and cytokine production in either candidemia patients or healthy controls. Based on these complementary in vitro and in vivo studies, it can be concluded that autophagy is redundant for the host response against systemic infections with C. albicans.
authors.affiliation: Department of Medicine, Radboud university medical center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands.
authors.forename: S P
authors.initials: SP
authors.lastname: Smeekens
authors.forename: R K
authors.initials: RK
authors.lastname: Malireddi
authors.forename: T S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: K
authors.initials: K
authors.lastname: Buffen
authors.forename: M
authors.initials: M
authors.lastname: Oosting
authors.forename: L A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: J R
authors.initials: JR
authors.lastname: Perfect
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: F L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: E
authors.initials: E
authors.lastname: van de Vosse
authors.forename: T-D
authors.initials: TD
authors.lastname: Kanneganti
authors.forename: M D
authors.initials: MD
authors.lastname: Johnson
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001343:Autophagy; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010587:Phagocytosis; D055815:Young Adult
chemical_list: D016207:Cytokines