Crosstalk at the initial encounter: interplay between host defense and ameba survival strategies

Abstract

The host-parasite relationship is based on a series of interplays between host defense mechanisms and parasite survival strategies. Progress has been made in understanding the role of host immune response in amebiasis. While host cells elaborate diverse mechanisms for pathogen expulsion, amebae have also developed complex strategies to modulate host immune response and facilitate their own survival. This paper will give an overview of current research on the mutual interactions between host and Entamoeba histolytica in human and experimental amebiasis. Understanding this crosstalk is crucial for the effective design and implementation of new vaccines and drugs for this leading parasitic disease.

Fig. 1. Modulation of macrophage functions by E. histolytica

The killing of E. hitolytica trophozoites by macrophages is mainly mediated by nitric oxide, derived from L-arginine by nitric oxide synthase (NOS). NO could inhibit amebic cysteine proteinases (CP) and alcohol dehydrogenase 2 (ADH2), the critical enzymes conferring virulence of E. histolytica. The arginase activity was detected in E. histolytica, which putatively converts L-arginine into L-ornithine, in turn limiting NO production by macrophage NOS. Prostaglandin E2 (PGE2) is an immunoregulatory molecule produced by cyclooxygenase (COX) in ameba or ameba-exposed macrophages. By activating cAMP-PKA pathway, PGE2 suppress macrophage effector functions by inhibiting PKC-mediated MHC-II expression and TNF-α production, while favoring IL-10 production. Monocyte Locomotion Inhibitory Factor (MLIF) produced by ameba may suppress macrophage functions in a manner similar to PGE2. Amebic lipophosphoglycan (LPG) might downregulate TLR2 expression on macrophages, thus control the effector mechanisms triggered through TLR2 signaling.

Fig 2. IgA anti-CRD is Associated with Immunity to E. histolytica Infection

Children with fecal IgA antibodies against the Gal/GalNAc lectin carbohydrate recognition domain (IgA anti-CRD (+); n = 81) had a lower incidence of new intestinal E. histolytica infection compared to children lacking this response (IgA anti-CRD (−); (n=149). The two groups were statistically significantly different (p ≤ 0.04) at every time point. The average duration of protection was 437 days (95% CI 346–528 days). (Haque et al. 2002, 2006).

Fig. 3. High Levels of IFN-γ Predict Increased Survival Free of E. histolytica Diarrhea

PBMCs were stimulated with soluble amebic extract and children grouped by IFN-γ production in response to SAE stimulation. Children were then followed for 44 months and incidence of E. histolytica diarrhea measured. Upper line and lower line indicate children with and without interferon gamma response above the median for all children (580 pg/ml) respectively. The two lines are significantly different: Logrank test p-value=0.03. n = 92 for the low IFN-γ, and n =103 for high IFN-γ groups (Haque et al 2006).