Temporary restoration of immune response againstToxoplasma gondiiin HIV-infected individuals after HAART, as studied in the hu-PBMC-SCID mouse model

Abstract

SUMMARYWe studied immune reconstitution against the parasite T. gondii in HIV-infected patients treated for 1 years with highly active antiretroviral therapy (HAART). We used SCID mice, humanized with peripheral blood mononuclear cells (PBMC) from patients, which were then infected with T. gondii cysts. Mice humanized with PBMC from patients before the start of HAART were highly susceptible to infection. In contrast, mice humanized with PBMC from patients who had received HAART for 6 months displayed higher survival rates, correlating with lower intracerebral parasite loads. However, this resistance was lost during follow up because mice humanized with PBMC from patients treated with HAART for 12 months survived for no longer than mice that had not been humanized. Specific lymphocyte proliferation assays showed that the increase in proliferative response depended on treatment duration and that HAART induced changes in IFN-g secretion in the presence of Toxoplasma antigens. Thus, our results indicate partial immune reconstitution against T. gondii in HIV-infected patients following HAART, possibly due to changes in the patterns of specific IFN-g production and redistribution of functional memory CD4 + cells.

Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS starting HAART

“…The results of our study, therefore, confirm that among patients with low CD4 cell counts (less than 200 CD4 T cells per ml), there is a profound defect in g-IFN production and lymphocyte proliferation in presence of T. gondii antigens [7,[14][15][16]. These patients should, therefore, receive a primary prophylaxis in order to prevent T. gondii reactivation.…”

“…Interestingly, we have found in our study that the restoration of effector memory CD4 T cells was associated with T. gondii-specific lymphocyte proliferation (Table 4). This finding is not unexpected, however, as effector memory dysfunction has been previously associated with susceptibility to opportunistic infections among HIV-infected patients [3,5,16,28,29]. Also, effector memory CD4 T cells are among CD4 T-cell Immune responses to T. gondii in HIV-infection Furco et al 2093 Table 2.…”

“…However, most studies addressing the issue of T. gondii prophylaxis discontinuation in patients with HIV infection have enrolled patients with CD4 T-cell counts above 200 cells/ ml for more than 8-12 months, with a median duration of HAART of 1-2 years and with a median CD4 T-cell counts at the enrolment usually above 300 cells/ml. Furthermore, no analysis of T. gondii-specific immune responses was performed in these studies and few data are available on the time course of T. gondii-specific immune reconstitution in patients with advanced HIV infection [7,[14][15][16].…”

Importance of Nonenteric Protozoan Infections in Immunocompromised People

“…As is the case with other protozoa, the availability of HAART has led to a major reduction in AIDS-associated toxoplasmosis (5,382,429). In particular, cases of Toxoplasma encephalitis have been greatly reduced to the extent that they are now very uncommon in regions with access to HAART (382, 429, 537).…”

Rapid discovery of inhibitors of Toxoplasma gondii using hybrid structure-based computational approach

“…Toxoplasmosis also ranks high among diseases that lead to morbidity and death in HIV/AIDS patients, particularly in the developing world. Re-emergence of toxoplasmosis as a life-threatening disease in HIV/AIDS patients is anticipated in the wake of emerging multi-drug resistant strains [3]. T. gondii is designated as an NIAID Category B biowarfare (priority) pathogen [4], in large part due to its danger to both humans and livestock, its persistence in the environment, and the ease with which it disseminates.…”