Pathogenic Th1 responses in CHIKV‐induced inflammation and their modulation upon Plasmodium parasites co‐infection

Abstract

The induction of polyarthritis and polyarthralgia is a hallmark of arthritogenic alphavirus infections, with an exceptionally higher morbidity observed with chikungunya virus (CHIKV). While the mechanisms underlying these incapacitating acute symptoms remain partially understood, the progression to chronic conditions in some cases remains unanswered. The highly pro‐inflammatory nature of alphavirus disease has suggested the involvement of virus‐specific, joint‐infiltrating Th1 cells as one of the main pathogenic mediators of CHIKV‐induced joint pathologies. This review summarizes the role of cell‐mediated immune responses in CHIKV pathogenesis, with a specific focus on pro‐inflammatory Th1 responses in the development of CHIKV joint inflammation. Furthermore, due to the explosive nature of arthritogenic alphavirus outbreaks and their recent expansion across the world, co‐infections with other highly prevalent pathogens such as malaria are likely to occur but the pathological outcomes of such interactions in humans are unknown. This review will also discuss the potential impact of malaria co‐infections on CHIKV pathogenesis and their relevance in alphavirus control programs in endemic areas.

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

“…Most of the top cytokines and transcriptional regulators ( Figure 4 ) are well described in the CHIKV literature, and as expected are dominated by interferon (IFN) and Th1 responses ( 1 , 15 , 40 , 41 , 54 , 60 , 63 – 66 ). Perhaps surprising is the absence of CCL2/CCR2 as an USR, even though CCL2 is a highly significant DEG, and is well described for CHIKV infections ( 45 , 55 , 67 ).…”

The Host Non-Coding RNA Response to Alphavirus Infection

“…CHIKV replication in fibroblasts and endothelial cells elicits the type I IFN response to the infection. Activation of the IFN response and its downstream signaling pathways leads to induction and secretion of the proinflammatory mediators, which is followed by infiltration of immune cells into the infected organs, especially joints, and inflammation leading to arthritis [ 49 , 163 , 164 ]. The chronic stage of CHIKV disease is characterized by musculoskeletal pain lasting for months or years.…”

Silent circulation of Chikungunya virus among pregnant women and newborns in the Western Brazilian Amazon before the first outbreak of chikungunya fever

“…The associations between not having IgG antibodies to CHIKV, being seropositive for antibodies to DENV and having reported gestational malaria were not expected, as the same low socioeconomic conditions should similarly increase the susceptibility to these three infections 17 . However, there are some studies in the literature on a possible “cross-protection” provided by an arbovirus infection in relation to the following one 18 - 20 , but so far, no pathophysiological mechanisms has been proposed.…”