African Enigma: Key Player in Human Immunodeficiency Virus Pathogenesis in Developing Countries?

Abstract

Recent data (10) show that enteric helminthic infections result in the secretion of type 2 cytokines (interleukin-4 [IL-4], IL-5, IL-6, IL-10) and a type 1-to-type 2 shift in cytokine profiles. The predominant production of type 2 cytokines is associated with a reduced incidence of gastritis and gastric atrophy in individuals who are coinfected with helminths and Helicobacter felis. The authors suggest that these results justify the low rate of gastric cancer observed in African individuals (the “African enigma”), a population in which helminthic infections are widespread. We are convinced that the importance of the African enigma goes well beyond the modulation of gastric cancer and that the cytokine profile observed in African individuals can justify the peculiarities that characterize human immunodeficiency virus (HIV) infection in Africa. To summarize: an abnormal activation of the immune system has repeatedly been postulated to be involved in the pathogenesis of African HIV infection (3); and data stemming from analyses performed over an extended period of time in the Gulu District of northern Uganda, where the prevalence of HIV infection ranges between 14 and 25%, confirm that lymphocytes from African HIV-infected individuals show functional and phenotypic signs of abnormal activation. Thus, the levels of tumor necrosis factor alpha (TNF-), gamma interferon (IFN-), and IL-10 production are increased when the level of cytokine production by antigen-stimulated peripheral blood mononuclear cells (PBMCs) of African HIV-infected individuals is compared to that of PBMCs of HIV-infected European patients; and the percentages of IL-10- and TNFproducing CD4 and CD8 cells in these individuals are increased (7, 17, 18). Additionally, the numbers of CD4 and HLA class II-expressing lymphocytes and the CD4 CD45ROCD4CD45RA ratio are augmented in African subjects compared to those in European subjects. Interestingly, immune activation in the African setting is not limited to HIV-infected individuals, as TNF-, IFN-, and IL-10 production is greatly augmented in individuals not infected with HIV as well (7). Immune activation in African subjects could result from environmental conditions, including parasitic infections, poor hygienic conditions, and dietary limitations, or could be the