A potential role for complement in immune evasion by Mycobacterium leprae.

Lepromatous leprosy is a model of immune evasion wherein pathogen-specific IL-10-secreting T cells and concomitant failure of Th-1 immunity permit uncontrolled proliferation of the intracellular pathogen, Mycobacterium leprae (M. leprae). The mechanism of this immune escape is unknown. Here, the authors report that phenolic glycolipid-1 (PGL-1), a major and distinguishing feature of the M. leprae cell wall, is expressed in the cell membrane of M. leprae-infected human dendritic cells, where it can activate complement in human serum. The authors demonstrate that PGL-1 and the C3 component of complement colocalize in lipid rafts in the dendritic cell membrane, and enter the immune synapse upon co-culture of M. leprae-infected DCs and T cells. Hence, activated C3 is strategically located to costimulate naïve T cells via the complement regulatory protein, CD46, a process known to stimulate the differentiation of IL-10-secreting regulatory T cells. These observations suggest a potential novel mechanism of immune evasion, wherein M. leprae may subvert host natural immunity to provoke an adaptive response that favors bacillary survival.

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.

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.

Necrobiotic xanthogranuloma associated with a benign monoclonal gammopathy.

Necrobiotic xanthogranuloma (NXG) is a disorder characterized by indurated, yellow-red nodules or plaques, primarily involving the face and, less frequently, the trunk and extremities. NXG may be associated with paraproteinemia, multiple myeloma, and hypertension. Histologically, xanthogranulomatous features with hyaline necrosis or necrobiosis are present. No first-line treatment has been established. This disease is a chronic process, and a patient's prognosis depends on the degree of extracutaneous involvement and the presence of visceral malignancies. We describe a patient with typical cutaneous and histologic findings of NXG with an associated monoclonal gammopathy.

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.

The human CD1-restricted T cell repertoire is limited to cross-reactive antigens: implications for host responses against immunologically related pathogens.

The repertoires of CD1- and MHC-restricted T cells are complementary, permitting the immune recognition of both lipid and peptide Ags, respectively. To compare the breadth of the CD1-restricted and MHC-restricted T cell repertoires, we evaluated T cell responses against lipid and peptide Ags of mycobacteria in leprosy, comparing tuberculoid patients, who are able to restrict the pathogen, and lepromatous patients, who have disseminated infection. The striking finding was that in lepromatous leprosy, T cells did not efficiently recognize lipid Ags from the leprosy pathogen, Mycobacterium leprae, or the related species, Mycobacterium tuberculosis, yet were able to efficiently recognize peptide Ags from M. tuberculosis, but not M. leprae. To identify a mechanism for T cell unresponsiveness against mycobacterial lipid Ags in lepromatous patients, we used T cell clones to probe the species specificity of the Ags recognized. We found that the majority of M. leprae-reactive CD1-restricted T cell clones (92%) were cross-reactive for multiple mycobacterial species, whereas the majority of M. leprae-reactive MHC-restricted T cells were species specific (66%), with a limited number of T cell clones cross-reactive (34%) with M. tuberculosis. In comparison with the MHC class II-restricted T cell repertoire, the CD1-restricted T cell repertoire is limited to recognition of cross-reactive Ags, imparting a distinct role in the host response to immunologically related pathogens.

Axillary polymastia.

"Polymastia" is a term used to describe the presence of more than 2 breasts in human beings. It is synonymous with supernumerary or accessory breast tissue. Accessory breast tissue has the potential to undergo the same benign and malignant changes as normal pectoral breast tissue.