Anne E. Burdick

Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells

Langerhans cells (LCs) constitute a subset of DCs that initiate immune responses in skin. Using leprosy as a model, we investigated whether expression of CD1a and langerin, an LC-specific C-type lectin, imparts a specific functional role to LCs. LC-like DCs and freshly isolated epidermal LCs presented nonpeptide antigens of Mycobacterium leprae to T cell clones derived from a leprosy patient in a CD1a-restricted and langerin-dependent manner. LC-like DCs were more efficient at CD1a-restricted antigen presentation than monocyte-derived DCs. LCs in leprosy lesions coexpress CD1a and langerin, placing LCs in position to efficiently present a subset of antigens to T cells as part of the host response to human infectious disease.

T-cell release of granulysin contributes to host defense in leprosy

A novel mechanism by which T cells contribute to host defense against microbial pathogens is release of the antimicrobial protein granulysin. We investigated the role of granulysin in human infectious disease using leprosy as a model. Granulysin-expressing T cells were detected in cutaneous leprosy lesions at a six-fold greater frequency in patients with the localized tuberculoid as compared with the disseminated lepromatous form of the disease. In contrast, perforin, a cytolytic molecule that colocalizes with granulysin in cytotoxic granules, was expressed at similar levels across the spectrum of disease. Within leprosy lesions, granulysin colocalized in CD4+ T cells and was expressed in CD4+ T-cell lines derived from skin lesions. These CD4+ T-cell lines lysed targets by the granule exocytosis pathway and reduced the viability of mycobacteria in infected targets. Given the broad antimicrobial spectrum of granulysin, these data provide evidence that T-cell release of granulysin contributes to host defense in human infectious disease.

Economic evaluation of telemedicine: review of the literature and research guidelines for benefit-cost analysis.

Telemedicine programs provide specialty health services to remote populations using telecommunications technology. This innovative approach to medical care delivery has been expanding for several years and currently covers various specialty areas such as cardiology, dermatology, and pediatrics. Economic evaluations of telemedicine, however, remain rare, and few of those conducted have accounted for the wide range of economic costs and benefits. Rigorous benefit-cost analyses of telemedicine programs could provide credible and comparative evidence of their economic viability and thus lead to the adoption and/or expansion of the most successful programs. To facilitate more advanced economic evaluations, this article presents research guidelines for conducting benefit-cost analyses of telemedicine programs, emphasizing opportunity cost estimation, commonly used program outcomes, and monetary conversion factors to translate outcomes to dollar values. The article concludes with specific recommendations for future research.

Divergence of macrophage phagocytic and antimicrobial programs in leprosy

Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.

Evidence for Human CD4+ T Cells in the CD1-Restricted Repertoire: Derivation of Mycobacteria-Reactive T Cells from Leprosy Lesions

Both the CD4−CD8− (double negative) and CD4−CD8+ T cell lineages have been shown to contain T cells which recognize microbial lipid and glycolipid Ags in the context of human CD1 molecules. To determine whether T cells expressing the CD4 coreceptor could recognize Ag in the context of CD1, we derived CD4+ T cell lines from the lesions of leprosy patients. We identified three CD4+ Mycobacterium leprae-reactive, CD1-restricted T cell lines: two CD1b restricted and one CD1c restricted. These T cell lines recognize mycobacterial Ags, one of which has not been previously described for CD1-restricted T cells. The response of CD4+ CD1-restricted T cells, unlike MHC class II-restricted T cells, was not inhibited by anti-CD4 mAb, suggesting that the CD4 coreceptor does not impact positive or negative selection of CD1-restricted T cells. The CD4+ CD1-restricted T cell lines produced IFN-γ and GM-CSF, the Th1 pattern of cytokines required for cell-mediated immunity against intracellular pathogens, but no detectable IL-4. The existence of CD4+ CD1-restricted T cells that produce a Th1 cytokine pattern suggests a contributory role in immunity to mycobacterial infection.

American Telemedicine Association's practice guidelines for teledermatology

The ATA assembled a group of experts to develop practice guidelines for teledermatology. This document represents the body of work that this distinguished group assembled. It was approved by the ATA Board of Directors and is presented here in its entirety.

Integrated Pathways for Neutrophil Recruitment and Inflammation in Leprosy

Neutrophil recruitment is pivotal to the host defense against microbial infection, but it also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by means of bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy and is characterized by neutrophil infiltration in lesions, the most overrepresented biological functional group was cell movement, including E-selectin, which was coordinately regulated with interleukin 1beta (IL-1beta). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1beta, which together with interferon gamma induced E-selectin expression on and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2 and Fc receptor activation, neutrophil migration, and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.

New-onset Majocchi’s granuloma in two kidney transplant recipients under tacrolimus treatment ☆ ☆☆ ★

In 1883, Majocchi first described an intracutaneous or subcutaneous granulomatous inflammation arising as a result of local invasion by a dermatophyte, which he called granuloma tricofitico. t The most common cause is Trichophyton rubrum. 2 Two types of Majocchis granuloma have been described, a perifollicular type secondary to trauma and a subcutaneous nodular type in immunocompromised hosts.2,3 We describe two

Resolution of Kaposi’s sarcoma associated with undetectable level of human herpesvirus 8 DNA in a patient with AIDS after protease inhibitor therapy ☆ ☆☆ ★ ★★

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Improvement of eumycetoma with itraconazole

Treatment of eumycetoma, both medical and surgical, is difficult and often unsuccessful. We describe a case of maduromycosis, 18 years in duration, with significant improvement after 6 months of itraconazole therapy.