Certainly, the selleck bio microflora in the gut of mice from different genetic backgrounds and from different animal facilities varies and could influence human engraftment in GALT and subsequently HIV transmission susceptibility. Besides potential differences in gut microflora, especially in BLT mice, gastrointestinal engraftment appears to be significantly better than the GALT engraftment we obtained in RAG2?/?��c?/? mice. BLT mice have the advantage of a human thymic tissue transplant, which could facilitate T-cell development. In our humanized mouse model, T-lymphocyte development occurs in the anlage of the murine thymus, which is almost completely repopulated with human cells. Nonetheless, the stroma of this thymus is of murine origin and may have unknown disadvantageous effects on overall lymphoid development.

Furthermore, to generate BLT mice, the NOD/SCID mouse strain was used. In contrast to RAG2?/?��c?/? mice, NOD/SCID mice do not have mutations or loss of ��c, the common gamma chain in receptors of multiple cytokines, including IL-7. Signaling through the IL-7 receptor is essential for formation of the Peyer’s patches’ anlagen (28), and humanized mice lacking this important feature may have more difficulties in repopulating the GALT than mice that have Peyer’s patches’ anlagen. To enrich for human cells of lymphoid origin in the rectal mucosa in our humanized mouse model, we induced local inflammation. Mucosal inflammation as seen in sexually transmitted diseases is a risk factor for HIV acquisition by increasing numbers of HIV target cells and disturbing epithelial integrity (14).

We treated humanized mice with Il-1�� rectally 24 h before HIV challenge. In untreated mice, no infections could be seen; in treated mice, 1/17 showed a detectable plasma viral load. Immunohistochemical analysis of Il-1��-treated uninfected mice suggests that, despite an inflammatory response and cell infiltration, human cell numbers were probably still too low to establish infection. It is believed that HIV first infects a local founder population in the lamina propria of the mucosal tissue and amplifies there Carfilzomib before systemic seeding and dissemination of the infection (16). In our model, local expansion of infection is difficult with only a few human cells present in the lamina propria. We only observed disseminated infection when mice were injected i.p. with HIV, and the mucosal amplification step was not needed. To attract human cells more efficiently to the GALT, we treated humanized mice with DSS, a compound widely used in murine models of inflammatory bowel disease. Repeated treatment with DSS leads to a chronic colitis with infiltration of lymphocytes and macrophages (21).