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

ABSTRACT: 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.

SUBMITTER: Preza GC

PROVIDER: S-EPMC3938918 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRecovery after colonic surgery is invariably delayed by disturbed gut motility. It is commonly assumed that colonic motility becomes quiescent after surgery, but this hypothesis has not been evaluated rigorously. This study quantified colonic motility through the early postoperative period using high-resolution colonic manometry.MethodsFibre-optic colonic manometry was performed continuously before, during and after surgery in the left colon and rectum of patients undergoing right hemicolectomy, and in healthy controls. Motor events were characterized by pattern, frequency, direction, velocity, amplitude and distance propagated.ResultsEight patients undergoing hemicolectomy and nine healthy controls were included in the study. Colonic motility became markedly hyperactive in all operated patients, consistently dominated by cyclic motor patterns. Onset of cyclic motor patterns began to a minor extent before operation, occurring with increasing intensity nearer the time of surgery; the mean(s.d.) active duration was 12(7) per cent over 3 h before operation and 43(17) per cent within 1 h before surgery (P = 0.024); in fasted controls it was 2(4) per cent (P < 0·001). After surgery, cyclic motor patterns increased markedly in extent and intensity, becoming nearly continuous (active duration 94(13) per cent; P < 0·001), with peak frequency 2-4 cycles per min in the sigmoid colon. This postoperative cyclic pattern was substantially more prominent than in non-operative controls, including in the fed state (active duration 27(20) per cent; P < 0·001), and also showed higher antegrade velocity (P < 0·001).ConclusionDistal gut motility becomes markedly hyperactive with colonic surgery, dominated by cyclic motor patterns. This hyperactivity likely represents a novel pathophysiological aspect of the surgical stress response. Hyperactive motility may contribute to gut dysfunction after surgery, potentially offering a new therapeutic target to enhance recovery.

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

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