Mechanism of Immune Evasion in Mosquito-Borne Diseases

Abstract

In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host's immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell's response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease.

Keywords: Rift Valley fever; West Nile fever; Zika; chikungunya; dengue; malaria; mosquito-borne diseases; virus.

Figure 1

Different pathogens involved in mosquito-borne diseases include Plasmodium, dengue virus, chikungunya virus, yellow fever virus, Zika virus, Rift Valley fever virus, Japanese encephalitis virus, and West Nile virus.

Figure 2

Plasmodium and infected red blood cells activate dendritic cells through parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) and are phagocytosed, and their antigens are presented to T cells. PRR signaling leads to the secretion of cytokines that initiate inflammation via Th1 and Th2 cell differentiation and macrophage polarization. Macrophages are responsible for the regulation of inflammation during the infection phase. T cells help with B cell differentiation and antibody secretion and secrete IFN-γ, which activates macrophages. IFN-γ-activated macrophages engulf opsonized cells.

Figure 3

The adaptive immune responses combine forces to fight the dengue virus. B cells produce antibodies that specifically recognize and neutralize the foreign viral particles, and cytotoxic T cells recognize and kill cells that are infected with the dengue virus.

Figure 4

Dengue and its link with other disease complications after dengue virus infection and disease severity.

Figure 5

Mosquito-borne viral diseases (West Nile, chikungunya, Zika, yellow fever, Japanese encephalitis, Rift Valley fever) are recognized as multi-organ diseases with a broad spectrum of manifestations. Post-acute viral syndromes persist, presenting with prolonged effects with post-disease multiorgan complications.

Figure 6

Representation of yellow fever (YF) pathway development. This figure illustrates the sequence of events in YF-related disease development, starting with the bite of an infected mosquito and ending with apoptosis and a heightened inflammatory reaction. The presence of the yellow fever virus (YFV) is indicated by a distinct color. It is hypothesized that intense viral replication in the liver sets off a series of molecular reactions, leading to considerable disruption in cytokine balance and an increased release of pro-inflammatory substances. Consequently, this results in substantial vascular impairment and multi-organ malfunction.