title: Protection from systemic Candida albicans infection by inactivation of the Sts phosphatases.
abstract: The human fungal pathogen Candida albicans causes invasive candidiasis, characterized by fatal organ failure due to disseminated fungal growth and inflammatory damage. The suppressor of TCR signaling 1 (Sts-1) and Sts-2 are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic cell lineages, including T lymphocytes, mast cells, and platelets. Functional inactivation of both Sts enzymes leads to profound resistance to systemic infection by C. albicans, such that greater than 80% of mice lacking Sts-1 and -2 survive a dose of C. albicans (2.5 × 10(5) CFU/mouse) that is uniformly lethal to wild-type mice within 10 days. Restriction of fungal growth within the kidney occurs by 24 h postinfection in the mutant mice. This occurs without induction of a hyperinflammatory response, as evidenced by the decreased presence of leukocytes and inflammatory cytokines that normally accompany the antifungal immune response. Instead, the absence of the Sts phosphatases leads to the rapid induction of a unique immunological environment within the kidney, as indicated by the early induction of a proinflammatory cytokine (CXL10). Mice lacking either Sts enzyme individually display an intermediate lethality phenotype. These observations identify an opportunity to optimize host immune responses toward a deadly fungal pathogen.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Shamoon
authors.initials: S
authors.lastname: Naseem
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Frank
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Konopka
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA nicholas.carpino@stonybrook.edu.
authors.forename: Nick
authors.initials: N
authors.lastname: Carpino
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; C482177:Sts-2 protein, mouse; D017027:Protein Tyrosine Phosphatases; C553497:TULA-2 protein, mouse