Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

Abstract

Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease.

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi

“…At this stage, the parasite tends to establish a trade‐off with the host mainly by using a complex network of antioxidant enzymes to shield itself from lysosomal oxygen and nitrogen reactive species (see Ref. ).…”

“…The effect of increased glucocorticoid levels during the acute phase of the disease ultimately favors parasitism and the establishment of a persistent infection (see Ref. ). The blockade of glucocorticoid receptors did not significantly affect parasitemia and the number of inflammatory foci in the heart, and only a tendency toward decrease in the number of amastigote nests was observed in both strains of mice.…”

“…In susceptible mice, the immune response to the parasite is not efficient enough for survival. This failure is mainly due to a deleterious excessive production of proinflammatory cytokines, which are protective only to certain extent . The increase in corticosterone levels induced by the immune response to T. cruzi serves most likely as a counter regulatory response to antagonize the mentioned deregulations.…”

Complement Factor H as a potential atherogenic marker in chronic Chagas’ disease

“…Different studies have demonstrated the crucial role of complement as a first line of defence against T. cruzi infection, as well as in the maintenance of chronic infection and severity of CCC . The complement system includes more than 35 plasma proteins/regulators and cell surface receptors which act together in the recognition and elimination of microbial and foreign cells.…”

“…in the maintenance of chronic infection 11 and severity of CCC. [12][13][14][15] The complement system includes more than 35 plasma proteins/regulators and cell surface receptors which act together in the recognition and elimination of microbial and foreign cells.…”