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Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense against disseminated candidiasis. 2006

Alieke G Vonk, and Mihai G Netea, and Johan H van Krieken, and Yoichiro Iwakura, and Jos W M van der Meer, and Bart Jan Kullberg
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

BACKGROUND Interleukin (IL)-1 alpha and IL-1 beta are protective proinflammatory cytokines involved in host defense against Candida albicans. It is, however, unknown whether they provide protection through similar mechanisms. We investigated the effect of endogenous IL-1 alpha and IL-1 beta on disseminated C. albicans infection. METHODS Mice deficient in the genes encoding IL-1 alpha (IL-1 alpha-/-), IL-1 beta (IL-1 beta-/-), or both molecules (IL-1 alpha-/- beta-/-) were used. Survival and C. albicans outgrowth in the kidneys was assessed after intravenous injection of C. albicans. RESULTS Both mortality and C. albicans outgrowth in the kidneys were significantly increased in IL-1 alpha-/- and IL-1 beta-/- mice, compared with those in control mice, with the IL-1 alpha-/- beta-/- mice being most susceptible to disseminated candidiasis. The host defense mechanisms triggered by IL-1 alpha and IL-1 beta differed from one another. IL-1 beta-/- mice showed decreased recruitment of granulocytes in response to an intraperitoneal C. albicans challenge, and generation of superoxide production was diminished in IL-1 beta-/- granulocytes. IL-1 alpha-/- mice had a reduced capacity to damage C. albicans pseudohyphae. Protective type 1 responses were deficient in both IL-1 alpha-/- and IL-1 beta-/- mice, as assessed by production of interferon-gamma by splenocytes in response to heat-killed C. albicans. CONCLUSIONS Although IL-1 alpha and IL-1 beta have differential effects on the various arms of host defense, both cytokines are essential for mounting a protective host response against invasive C. albicans infection.

UI MeSH Term Description Entries
D007121 Immunocompetence The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. Competence, Immunologic,Immunologic Competence,Immunological Competence,Competence, Immunological
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002176 Candida albicans A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis). Candida albicans var. stellatoidea,Candida stellatoidea,Dematium albicans,Monilia albicans,Myceloblastanon albicans,Mycotorula albicans,Parasaccharomyces albicans,Procandida albicans,Procandida stellatoidea,Saccharomyces albicans,Syringospora albicans
D002177 Candidiasis Infection with a fungus of the genus CANDIDA. It is usually a superficial infection of the moist areas of the body and is generally caused by CANDIDA ALBICANS. (Dorland, 27th ed) Candida Infection,Moniliasis,Candida Infections,Candidiases,Infection, Candida,Moniliases
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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