Host Intracellular Signaling Events and Pro-inflammatory Cytokine Production in African Trypanosomiasis

Abstract

Pathogens, such as bacteria, viruses, and parasites, possess specific molecules or proteins that are recognized by several host innate immune receptors, leading to the activation of several intracellular signaling molecules and pathways. The magnitude and quality of these events significantly affect the outcome of infection. African trypanosomes, including Trypanosoma congolense, are capable of manipulating the host immune response, including the activity of macrophages, which are the key immune cells that contribute to the immunopathogenesis of African trypanosomiasis. Although it is known that immune hyperactivation and excessive pro-inflammatory cytokine production are the hallmarks of African trypanosomiasis, the mechanisms through which these events are triggered are poorly defined. However, it is known that macrophages may play a significant role in these processes, because phagocytosis of trypanosomes by macrophages initiates intracellular signal transduction cascades that lead to the release of pro-inflammatory cytokines and alteration in cell function. This review highlights recent progress in our understanding of the innate immune receptors, signaling pathways, and transcription factors involved in T. congolense-induced pro-inflammatory cytokine production in macrophages. It will reveal the existence of complex signaling events through which the parasite modulates the host immune response, thus identifying novel targets that could aid in designing strategies to effectively control the disease.

To the Skin and Beyond: The Immune Response to African Trypanosomes as They Enter and Exit the Vertebrate Host

“…The induction of type 2 macrophages is a prominent feature of the immunosuppression that occurs during chronic T. brucei infections. Studies have shown that trypanosomes trigger a switch in macrophage activation from pro-inflammatory (or classically-activated) cells to a more anti-inflammatory (or alternatively activated) state (74, 104,110,136,137). This switch in macrophage character skews the host immune response from Th1 to Th2, resulting in an anti-inflammatory environment that promotes parasite survival in the host (138).…”

Interferon Gamma in African Trypanosome Infections: Friends or Foes?

“…In addition, an estimated three million cattle die from this disease each year, resulting in economic loss of four billion US dollars in Africa ( 5 ). Following malaria and schistosomiasis, African trypanosomiasis is the third significant contributor to the global burden of parasitic diseases ( 6 ). The causative agents of this disease are various species of protozoan parasites belonging to genus of Trypanosoma .…”

“…The causative agents of this disease are various species of protozoan parasites belonging to genus of Trypanosoma . Among them, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense infect humans, while Trypanosoma brucei brucei, Trypanosoma congolense , and Trypanosoma vivax are the major species causing animal infections ( 6 ).…”

Anti-Inflammatory Effect of <i>o</i>-Vanillic Acid on Lipopolysaccharide-Stimulated Macrophages and Inflammation Models

“…The hallmark of initial inflammation is increased vascular permeability, blood flow, and leukocytosis at the injured tissue site [3]. During an inflammatory response, intracellular signal events, driven by pro-inflammatory mediators and cytokines, are activated [4]. Among immune cells, macrophages play a major role in the inflammatory responses through the production of various mediators such as nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and pro-inflammatory cytokines [5].…”