HIV infection and the gut: scarred for life?

نویسندگان

  • Sarah W Read
  • Irini Sereti
چکیده

Over the past decade, the gut-associated lymphocytes have been shown to play a critical role in the early pathogenesis of HIV infection. Because of constant exposure to foreign antigens, the gut contains an abundance of activated effector memory CD4 T cells that express CCR5 and are highly susceptible to HIV infection [1]. Primary HIV infections and simian immunodeficiency virus (SIV) infections lead to rapid and profound depletion of these cells [2– 4], which is more pronounced than the depletion in peripheral blood or other lymphoid tissue and persists throughout the course of untreated infection. The administration of antiretroviral therapy during chronic infection is highly effective in increasing the number of CD4 T cells and decreasing the proportion of activated T cells in peripheral blood. However, significant delay in CD4 T cell restoration may be seen in the gut, particularly in the lamina propria [5]. Despite the slow or incomplete resolution of the profound abnormalities seen in the gut mucosa of HIV-infected patients, a clear connection to clinical outcome in humans is still missing. The pathogenesis of HIV infection is characterized by CD4 T cell immunodeficiency in the context of generalized immune activation and dysregulation. T cells with an activated phenotype have been associated with CD4 T cell decline in peripheral blood, as well as with clinical disease progression [6, 7]. However, the exact mechanisms leading to this pathogenic immune activation remain unclear. One possible mechanism linking the effects of HIV in the gut to generalized immune activation has recently been postulated. Brenchley et al. [8] have shown that the bacterial cell wall component lipopolysaccharide (LPS) is elevated in the peripheral blood of individuals chronically infected with HIV, and the plasma level of LPS directly correlates with an increased proportion of circulating activated CD8 T cells. These findings led to the hypothesis that dysfunction of the gastrointestinal mucosa leads to translocation of bacterial products and results in generalized immune activation. However, data from the nonpathogenic SIV–sooty mangabey model show that CD4 T cell depletion is not sufficient to result in high LPS levels, which suggests that additional insults are required [9]. In this issue of the Journal, Estes et al. [10] report on collagen deposition in the gastrointestinal tract as another potential mechanism that contributes to T cell depletion and/or limits CD4 T cell restoration in the gut. Previously, these authors reported that early fibrosis from collagen deposition resulted in disruption of the lymphatic tissue in the lymph nodes of HIV-infected individuals and was predictive of the magnitude of change in peripheral CD4 T cell counts after up to 3 years of antiretroviral therapy [11–13]. They have postulated that the fibrosis found in lymph nodes is detrimental to survival, growth, and trafficking of CD4 T cells through various mechanisms including physical constraint, cell-cell interactions, and access to cytokines. In the Estes et al. [10] article, they report on the extent of collagen deposition in Peyer patches and its potential association with immune restoration in this compartment, as compared with that in lymph nodes and peripheral blood. In this study, uninfected individuals and HIV-infected individuals at various stages of disease underwent sampling of lymph nodes, ileum, and peripheral blood. A subset of infected participants began antiretroviral therapy and was sampled again, 6 months after initiation of therapy. At baseline, significant depletion of CD4 T cells was observed for all compartments in HIV-infected participants, with a comparatively greater reduction in gut lymphoid tissue, although participants who did not initiate therapy were excluded from this analysis. Despite increases in the population of circulating CD4 T cells after 6 months of antiretroviral therapy, there were no significant increases in the total population of CD4 T cells in lymphoid tissue. Received 6 May 2008; accepted 6 May 2008; electronically published 3 July 2008. Potential conflicts of interest: none reported. Reprints or correspondence: Sarah Read, MD, DAIDS, 6700B Rockledge Dr., Rm 5111, Bethesda, MD 20892 ([email protected]). The Journal of Infectious Diseases 2008; 198:453–5 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19804-0001$15.00 DOI: 10.1086/590113 E D I T O R I A L C O M M E N T A R Y

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عنوان ژورنال:
  • The Journal of infectious diseases

دوره 198 4  شماره 

صفحات  -

تاریخ انتشار 2008