More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

Although helminth-Plasmodium coinfections are common in tropical regions, the implications of this co-existence for the host immune response are poorly understood. In order to understand the effect of helminth infection at different times of coinfection on the immune response against Plasmodium infection, BALB/c mice were intraperitoneally infected with Taenia crassiceps (Tc). At 2 (Tc2) or 8 (Tc8) weeks post-infection, mice were intravenously infected with 1 × 10 Plasmodium yoelii (Py) 17XL-parasitized red blood cells. Py 17XL-single-infected mice developed cachexia, splenomegaly, and anemia, and died at 11 days post-infection. Importantly, Tc2 + Py-coinfected mice showed increased survival of 58% on day 11, but developed pathology (cachexia and splenomegaly) and succumbed on day 18 post-coinfection, this latter associated with high levels of IL-1β and IL-12, and reduced IFN-γ in serum compared with Py 17XL-single-infected mice. Interestingly, Tc8 + Py-coinfected mice showed increased survival up to 80% on day 11 and succumbed on day 30 post-coinfection. This increased survival rate conferred by chronic helminth infection was associated with a decreased pathology and mixed inflammatory-type 1/anti-inflammatory-type 2 immune profile as evidenced by the production of high levels of IL-12 and IL-10, and reduced TNF-α from macrophages, high levels of IL-4 and IL-10, and low levels of IFN-γ from spleen cells. Also high serum levels of IL-1β, TNF-α, IL-12, IL-4, and IL-10, but a significant reduction of IFN-γ were observed. Together, these data indicate that polarization of the cell-mediated response modulated by a pre-existing helminth infection differentially impacts on the host immune response to Py 17XL in a time-dependent manner.

Macrophage migration inhibitory factor (MIF) is a cytokine recognized regulator of the inflammatory immune response associated with several immune cells that produce inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-18, and TNF-α. This study aimed to understand the effect of MIF on the immune response and pathogenesis during Plasmodium infection. Wild-type (Wt) and MIF knockout (Mif-/-) mice were intravenously infected with 1×103Plasmodium yoelii (Py) 17XL-parasitized red blood cells. Our data showed that Py17XL-infected Wt mice died 11 days postinfection, while Mif-/- mice showed reduced parasitemia and an increase in their survival at day 11 up to 58%, importantly they succumb up to day 21 postinfection. The increased survival rate in Mif-/- mice was associated with less severe cachexia and anemia as a result of a mixed Th1/Th2 cytokine profile, high levels of IL-12, IL-17/IL-4, and IL-10 in serum; and high levels of IL-4 and IL-10, and low levels of IFN-γ in spleen cells compared to Py17XL infected Wt mice. Moreover, macrophages (Mφs) from Mif-/- mice exhibited higher concentrations of IL-10 and IL-12 and reduced levels of TNF-α and nitric oxide (NO) compared to Py17XL-infected Wt mice. These results demonstrate that MIF has an important role in regulating the immune response associated with host pathogenesis and lethality, which is relevant to consider in preventing/reducing complications in Plasmodium infections.