Candida 2014

Well, Nephew David is publishing something on the way to his doctorate.  That is David Frank.  The other Nephew David published a book which I haven't finished yet. (A commentary on the Talmud tractate Shabbat.)

This will appear in  Infection and Immunity this month.  Infect. Immun. IAI.02789-14; published ahead of print 24 November 2014,

Protection from systemic Candida albicans infection by inactivation of the Sts phosphatases

 Shamoon Naseem a, David Frank a,b,  James B. Konopka a and  Nick Carpino a

 

 Author Affiliations

Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA a. 

Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, USA b. 

 

ABSTRACT

 

The human fungal pathogen Candida albicans causes invasive candidiasis, characterized by fatal organ failure due to disseminated fungal growth and inflammatory damage. Suppressor of TCR Signaling (Sts) – 1 and – 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 × 105 CFU/mouse) that is uniformly lethal to wild-type mice within 10 days. Restriction of fungal growth within the kidney occurs by 24 hours post infection in the mutant mice. This occurs without induction of a hyper-inflammatory response, as evidenced by the decreased presence of leukocytes and inflammatory cytokines that normally accompany the anti-fungal 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 pro-inflammatory 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.