title: Strain differences in the immune mechanisms of resistance of immunocompetent rats to pulmonary aspergillosis.
abstract: Although the relevance of genetically-based variations in susceptibility to pulmonary aspergillosis was shown in immunocompromised mice and is indicated in humans, there is virtually no information concerning variations in antifungal immune responses in resistant individuals. We have shown recently the relevance of proinflammatory cytokine (interferon-γ/IFN-γ and interleukin-17/IL-17) responses in resistance to sublethal Aspergillus fumigatus infection of non-suppressed Dark Agouti (DA) rats (strain known of a substantial immune reactivity to noxious insults). In this study, anti-fungal immune activities of leukocytes recovered from lungs by enzyme digestion (phagocytosis, oxidative activity, hyphal killing, CD11b expression, as well as production of IFN-γ, IL-17 and Th2/anti-inflammatory cytokines interleukin-4/IL-4 and interleukin-10/IL-10) were investigated in less reactive Albino Oxford (AO) and compared to DA rats. Elimination of fungus from lungs of AO rats was associated with lower degree of leukocyte infiltration and of the majority of their basic effector activities in comparison to DA rats. Lower production of IFN-γ by pulmonary leukocytes was observed early (day 1) post infection (p.i.) in AO compared to DA rats, but without changes in IL-4. Both strains responded to infection by an increase of IL-17 and IL-10, but production of cytokines was higher (from days 7 p.i. and 3 p.i. for IL-17 and IL-10, respectively) in AO compared to DA rats. The levels and pattern of IFN-γ and IL-4 responses by draining lymph node (dLN) cells were similar in both strains and basically corresponded to those of lung leukocytes. In contrast, similar levels of draining lymph node cell production of IL-17 and IL-10 were observed in both strains with lack of changes in mRNA, what suggests additional stimulation of these cytokines in lungs of AO rats. The knowledge of strain differences in the immune-based strategies in response of immunocompetent hosts to A. fumigatus might contribute to our understanding of variations in underlying mechanisms that enable of resistance to this fungus.
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Demenesku
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Popov Aleksandrov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ninkov
authors.affiliation: Department of Plant Physiology (Mycology Lab), Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana142, 11060 Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Glamoclija
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia; Institute of Zoology, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia; Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia. Electronic address: milena@ibiss.bg.ac.rs.
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D055732:Pulmonary Aspergillosis / Q000276:immunology* / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
chemical_list: C515934:Il17a protein, rat; D020381:Interleukin-17; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: A. fumigatus pulmonary infection; AO and DA rats; IFN-γ; IL-(17, 4, 10); Lung leukocytes