Monocyte Trafficking In and Antimicrobial Defense

The term ‘monocyte’ refers to a subset of circulating white blood cells that differentiate into a range of tissue macrophages and dendritic cells. Bloodstream monocytes derive from precursors in the bone marrow and are subdivided into subsets that differ in size, trafficking, innate immune receptor expression and in their ability to differentiate following stimulation. Our laboratory investigates inflammatory monocytes, a subset that mediates host antimicrobial defenses but also enhances tissue destruction during some infections.

VRE Colonization and Infection

Antibiotic-resistant bacteria are an increasing problem in hospitalized patients and commonly cause infections following broad-spectrum antibiotic administration. Among these, Vancomycin-resistant Enterococcus (VRE), is one of the most common causes of bloodstream infections. Our laboratory demonstrated that treatment of mice with antibiotics dramatically increases susceptibility to colonization with VRE.

Clostridium Difficile Infection

Clostridium difficile is a Gram positive, spore-forming rod that causes a spectrum of intestinal diseases extending from relatively mild diarrhea to toxic megacolon and is a frequent cause of hospital-acquired enteric infection. C. difficile associated disease (CDAD) generally occurs in hospitalized patients and almost always follows antibiotic treatment for unrelated infections.

Antibiotics and Microbiota in Mice and Humans

Antibiotics vary in their specificity and thus can be used to selectively eliminate bacterial populations that inhabit mucosal surfaces. We have characterized antibiotic-induced changes in the intestinal microbiota and the impact on susceptibility to intestinal colonization with VRE. Many questions about the relationship between the intestinal microbiota and the innate and adaptive immune systems remain unanswered and are the focus of experiments in our laboratory.

CD4 T Cell Responses to Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is one of the most important pathogens infecting humans. Although the immune response to Mtb has been extensively investigated, generation of an effective vaccine has been frustratingly difficult.