Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic mucosa defined by CD207 dendritic cells and CD209 macrophages.

A common route for HIV-1 infection is sexual transmission across colorectal mucosa, which is thought to be 10-2,000 times more vulnerable to infection than that of the female genital tract. Mucosal surfaces are the first line of defense against many pathogens but the antigen-presenting cells (APCs), key regulators of innate immunity and determinants of adaptive immunity, are not well defined in these target tissues. Using immunohistochemistry, dendritic cells expressing Langerin (CD207(+)), a lectin known to bind and internalize HIV-1, were detected in the periphery of colonic glands and sparsely scattered in the submucosa similarly in colorectal mucosa. This cell type, well known in skin, has generally not been reported in colonic/rectal mucosa. Unexpectedly, the largest APC population observed was a macrophage-like population expressing the well-characterized tissue macrophage markers CD68 and CD163. Confocal microscopy of these cells revealed colocalization of CD209 (DC-SIGN), a presumed dendritic cell marker believed to facilitate HIV-1 transmission, but not other dendritic cell markers. These results show evidence of the unconfirmed presence of Langerhans cells in colorectal mucosa and a predominance of macrophage-like APCs that express CD209 (DC-SIGN). These findings define potential target cells in the pathogenesis of HIV-1 transmission, which may have key implications for the study of early transmission events in normal colorectal mucosa, as well as other infectious diseases and primary immune diseases involving the gut.