Tim3 binding to galectin-9 stimulates antimicrobial immunity

The interaction between Tim3 on Th1 cells and galectin-9 on Mycobacterium tuberculosis–infected macrophages restricts the bacterial growth by stimulating caspase-1–dependent IL-1β secretion

Preventing Infection and Biofilm Formation on Surface Modified Orthopedic Implants

Contamination of combat trauma wounds with environmental residues can lead to bacterial infection of orthopedic fractures, which causes delay and difficulties in patient treatment. The reported infection rate of the improvised explosive devices (IED) injuries is 91%, and biofilm formation on orthopedic implants can lead to chronic infection with a rate of 40% in fracture wounds. Once the biofilm is formed it becomes resistant to antibiotics, so designing orthopedic implants that can self-regulate local infection and biofilm formation is beneficial for these patients. Polytetrafluoroethylene (PTFE) and biodegradable chitosan with local antibiotic (vancomycin) elution were deposited on the stainless steel and titanium implant samples (coupons) to reduce biofilm formation and bacterial infection. Staphylococcus aureus is the most common pathogen associated with orthopedic implant infections. S. aureus Seattle 1945 (ATCC 25923) strain encoding intracellular GFP was used to evaluate the antimicrobial and anti-biofilm properties of the modified metal coupons using methods such as crystal violet analysis, ultrasound water bath with viable cell counts and confocal laser scanning microscopy. The release rate of vancomycin from the coupons was determined by HPLC analysis of collected leachates from surface modified coupons. In vitro studies of antibacterial properties of the coupons showed that PTFE did not provide significant advantages against biofilm formation, but the incorporation of chitosan and vancomycin onto modified surfaces prevented biofilm formation on the coupons. LCSM scanning of the modified surfaces with vancomycin did not detect any GFP signal from these coupons and no bacterial cell was recovered from the vancomycin treated surfaces. Local drug-release profile of antibiotic doped chitosan showed the concentration of local vancomycin released within the first 48 hours was effective in preventing bacterial attachment onto the coupons. Based on data obtained from these in vitro studies, it is concluded that vancomycin treated coupons were able to successfully prevent biofilm formation and bacterial growth on the modified surfaces

Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function

Abetalipoproteinemia (ABL) is a rare Mendelian disorder of lipid metabolism due to genetic deficiency in microsomal triglyceride transfer protein (MTP). It is associated with defects in MTP-mediated lipid transfer onto apolipoprotein B (APOB) and impaired secretion of APOB-containing lipoproteins. Recently, MTP was shown to regulate the CD1 family of lipid antigen-presenting molecules, but little is known about immune function in ABL patients. Here, we have shown that ABL is characterized by immune defects affecting presentation of self and microbial lipid antigens by group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 molecules. In dendritic cells isolated from ABL patients, MTP deficiency was associated with increased proteasomal degradation of group 1 CD1 molecules. Although CD1d escaped degradation, it was unable to load antigens and exhibited functional defects similar to those affecting the group 1 CD1 molecules. The reduction in CD1 function resulted in impaired activation of CD1-restricted T and invariant natural killer T (iNKT) cells and reduced numbers and phenotypic alterations of iNKT cells consistent with central and peripheral CD1 defects in vivo. These data highlight MTP as a unique regulator of human metabolic and immune pathways and reveal that ABL is not only a disorder of lipid metabolism but also an immune disease involving CD1