Helminth Parasites Alter Protection against Plasmodium Infection

Figure 3

Concomitant helminth infection modified the immune response and susceptibility to Plasmodium infection. Helminth parasites have developed complicated strategies to infect and successfully colonize their host. (1) In an acute helminth infection, an initial Th1-like immune response (i.e., IFN-γ, IL-12, and classical activation macrophage (CAM)) is associated with low parasite growth. (2) However, as the parasite colonizes the host, the immune response rapidly shifts toward a Th2-dominant response (IL-4, IL-5, IL-10, IL-13, and AAM) in parallel with increased helminth parasitemia. (3) This “immune environment” determined by helminth infection modifies the immune response and the susceptibility to Plasmodium. That is, acutely helminth-infected mice exhibited (2) decreased transmission of Plasmodium (2.1), decreased parasitemia and increased survival (2.2) due to high levels of IFN-γ and TNF- in the early stage. However, this immune response increased mortality during the chronic stage of malaria (2.3) and increased severe pathology, such as ECM and severe malaria anemia (SMA) (2.4). In contrast, chronically helminth-infected mice (3) increased the transmission of Plasmodium (3.1), parasitemia and mortality (3.2) due to high levels of IL-4, IL-10, and TGF-β and low levels of IFN-γ and TNF-. However, during the course of the coinfection, the Th1 response against Plasmodium was increased. In fact, a mixed Th1/Th2 response during the chronic stage induced low levels of parasitemia and was asymptomatic (3.3). Interestingly, chronic helminth infections inhibited severe pathologies caused by Plasmodium, such as ECM and SMA (3.4), and increased the survival due to a decreased inflammatory response. Abbreviations: Schistosoma mansoni (Sm), Heligmosomoides polygyrus (Hp), Echinostoma caproni (Ec), Strongyloides ratti (Sr), Nippostrongylus brasiliensis (Nb), Litomosoides sigmodontis (Ls), Brugia pahangi (Bp), and Trichinella spiralis (Ts).