Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression

Abstract

Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways.

Ellagic acid reduces murine schistosomiasis mansoni immunopathology via up-regulation of IL-10 and down-modulation of pro-inflammatory cytokines production

“…Numerous studies, reviewed in 78 , have showed an active immuneregulatory role of antibodies from infected individuals. Immune complexes from the blood of infected patients were able to inhibit in vitro granuloma formation.…”

“…In the murine model of schistosomiasis, several Th1, Th2 and Th17 as well as pro-inflammatory cytokines (such as IL-1b, IL-12 and TNF-a) regulate both granuloma formation and hepatic fibrosis 77,78 . Therefore, tight regulation of these cytokine responses generated during schistosome infection is essential to prevent excessive pathology.…”

A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection

“…As helminth infections are generally chronic, further studies are required to determine whether soluble proteins released from schistosome eggs trapped in the liver have long‐term immunomodulatory effects on the ability of hepatic cDCs to initiate and maintain adaptive immune responses. This will be particularly important for understanding the potential negative impact of helminths on immune responses to vaccines and other major pathogens that coexist in schistosome endemic areas 46 …”

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

“…During the chronic phase of intestinal schistosomiasis, disease morbidity has been associated mostly with the type and intensity of the granulomatous inflammatory response induced by egg‐secreting antigens that become trapped in venules in the host's tissues, especially in the liver and intestine . Granuloma formation and modulation are dynamic processes that lead to the sequential recruitment and accumulation of immune cells around the trapped Schistosoma egg, mediated by a local production of immune mediators, such as cytokines and chemokines . The granuloma induced by parasite eggs causes the confinement of the parasite antigens, thereby protecting the host tissue from their cytotoxic effect.…”