Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.
Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.
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DOI：
10.1097/qai.0b013e3182898392
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发表时间：
2013-07-01
期刊：
影响因子：
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通讯作者：
NIAID HIV Vaccine Trials Network
中科院分区：
文献类型：
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作者：
McElrath MJ;Smythe K;Randolph-Habecker J;Melton KR;Goodpaster TA;Hughes SM;Mack M;Sato A;Diaz G;Steinbach G;Novak RM;Curlin ME;Lord JD;Maenza J;Duerr A;Frahm N;Hladik F;NIAID HIV Vaccine Trials Network
预防艾滋病毒直肠传播是疫苗和局部杀微生物剂的高度优先目标，因为很大一部分艾滋病毒传播发生在直肠。然而，除了从结肠做出的推断外，人们对人类直肠中特定的靶细胞环境知之甚少。我们对29名健康人肛管近端4 cm和30 cm处的HIV靶细胞(表达CCR5的T细胞、巨噬细胞和树突状细胞)进行了全面的比较原位荧光研究，使用数字化组合染色的计算机分析。最引人注目的是，我们发现直肠中表达HIV共同受体CCR5的CD68+巨噬细胞是结肠的三倍多(p=0.0001)，因此，在生物学上，直肠巨噬细胞似乎更接近阴道中对HIV敏感的CCR5高表型，而不是结肠中主要抵抗HIV的CCR5低表型。与直肠相比，假定的CD209+树突状细胞在结肠中通常较丰富(p=0.0004)，尽管它们在两个间隔中的CCR5表达水平相似。CD3+T细胞密度和CCR5在结肠和直肠中的表达水平相似。我们的研究建立了人类远端肠道中HIV感染的靶细胞环境，并大体上证明了结肠和直肠是免疫上不同的解剖分区。CCR5在直肠巨噬细胞上的较高表达表明，肠道的最远端可能特别容易受到艾滋病毒感染。我们的发现还强调，在将从结肠组织获得的数据外推到直肠时应谨慎行事。
Prevention of rectal HIV transmission is a high priority goal for vaccines and topical microbicides because a large fraction of HIV transmissions occurs rectally. Yet, little is known about the specific target cell milieu in the human rectum other than inferences made from the colon. We conducted a comprehensive comparative in situ fluorescence study of HIV target cells (CCR5-expressing T cells, macrophages and putative dendritic cells) at 4 and 30 cm proximal of the anal canal in 29 healthy individuals, using computerized analysis of digitized combination stains. Most strikingly, we find that more than three times as many CD68+ macrophages express the HIV co-receptor CCR5 in the rectum than the colon (p=0.0001), and as such rectal macrophages appear biologically closer to the HIV-susceptible CCR5high phenotype in the vagina than the mostly HIV-resistant CCR5low phenotype in the colon. Putative CD209+ dendritic cells are generally enriched in the colon compared to the rectum (p=0.0004), though their CCR5 expression levels are similar in both compartments. CD3+ T cell densities and CCR5 expression levels are comparable in the colon and rectum. Our study establishes the target cell environment for HIV infection in the human distal gut and demonstrates in general terms that the colon and rectum are immunologically distinct anatomical compartments. Greater expression of CCR5 on rectal macrophages suggests that the most distal sections of the gut may be especially vulnerable to HIV infection. Our findings also emphasize that caution should be exercised when extrapolating data obtained from colon tissues to the rectum.