Long chikungunya? An overview to immunopathology of persistent arthralgia

Figure 2 Hypothesis for persistent arthralgia caused by Chikungunya virus infection. During the initial viremia phase, interferon gamma stimulates increased expression of the signaling lymphocytic activation molecule family member 7 receptor in macrophages, which persists into the chronic phase due to continuous stimulation by Tumor necrosis factor-alpha. Activation of the signaling lymphocytic activation molecule family member 7 receptor and persistence of viral antigens (RNA) enable macrophages to sustain a state of chronic inflammatory over-activation, perpetuating the release of cytokines that facilitate the formation of an inflammatory microenvironment, tissue damage, and clinical deterioration. SLAMF7: Signaling lymphocytic activation molecule family member 7; LTCD4: CD4 T lymphocytes; CCL: C-C motif ligand; NK: Natural killer; TNF-α: Tumor necrosis factor-alpha; IL: Interleukin; APC: Antigen presenting cells; IFN-γ: Interferon gamma.