The schistosoma granuloma: friend or foe?

Abstract

Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4(+) T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection.

Keywords: Schistosoma mansoni; fibrosis; granuloma; immunology; inflammation.

Figure 1

Representative histology sections (stained with H&E) of livers from a CD4⁺ T cell depleted (A) and normal (B) mouse, with arrows to indicate the S. mansoni egg.

Figure 2

Graphical representation of the cell populations involved in the formation of the S. mansoni egg-induced liver granuloma from an immune suppressed (left) and immunologically intact mouse (right).

Figure 3

Images of livers from an uninfected (A), an S. mansoni-infected immune competent (B), and immune suppressed (C) mouse. While an infected immunologically intact mice has granulomas in the liver (B), in an immunodeficient mouse (C) there is marked whitening of the liver due to microvesicular hepatosteatosis.