SAAG‐4 is a novel mosquito salivary protein that programmes host CD4⁺ T cells to express IL‐4

Abstract

Mosquitoes represent the most important vector for transmitting pathogens that cause human disease. Central to pathogen transmission is the ability to divert the host immune system away from Th1 and towards Th2 responsiveness. Identification of the mosquito factor(s) critical for programming Th2 responsiveness should therefore lead to strategies to neutralize their function and thus prevent disease transmission. In the current study, we used a TCR transgenic adoptive transfer system to screen gene products present in the saliva of the mosquito Aedes aegypti for their ability to program CD4 T cells to express the signature Th2 cytokine IL-4. The clone SAAG-4 encodes a secreted protein with a predicted size of 20 kDa whose function has previously been uncharacterized. Notably, SAAG-4 reduced host CD4 T cell expression of the signature Th1 cytokine IFN-γ while simultaneously increasing expression of IL-4. SAAG-4 is therefore the first identified mosquito factor that can program Th2 effector CD4 T cell differentiation.

Biomarkers of Vector Bites: Arthropod Immunogenic Salivary Proteins in Vector-Borne Diseases Control

“…In Ae. aegypti saliva, a protein of 20 kDa is able to induce a Th2 response by the production of interleukin-4 in CD4 + cells, while reducing the expression the Th1 response by decreasing the production of interferon-γ (Boppana et al 2009). …”

Immune responses of the domestic fowl to Dermanyssus gallinae under laboratory conditions

“…Tick saliva has been shown to modify host cytokine and chemokine responses, down-regulating Th1 cell activity such as Natural killer cells and macrophage responses and stimulating a Th2 response (Wikel 1996;Kopecký and Kuthejlová 1998;Christe et al 1999;Brossard and Wikel 2004;Vančová et al 2007). Modulation of host immune responses to facilitate unhindered feeding in ticks is an obvious strategy for parasites remaining on the host for prolonged periods, but it has less obvious relevance for temporary blood feeders such as mosquitoes and mites (Boppana et al 2009;Jackson et al 2009). …”

Immunological consequences of arthropod vector‐derived salivary factors

“…Arthropod saliva contains various vasodilators and inhibitors for a broad spectrum of host functions [26] such as blood clotting (to facilitate feeding), mast cell activation (to prevent degranulation and cytokine secretion), complement activation and neutrophil activation (to control immediate responses to the process of blood feeding). Some mosquito saliva molecules interfere with adaptive immune responses by inhibiting the proliferation of B cells and T cells [27] (a phenomenon also reported for the saliva of black flies [28]), and selectively suppressing Th1-type cytokine responses but not Th2-type responses [21,27,29]. A Th2-polarization of immune responses has been reported not only for mosquito [29], but also tick saliva [30,31].…”

“…Some mosquito saliva molecules interfere with adaptive immune responses by inhibiting the proliferation of B cells and T cells [27] (a phenomenon also reported for the saliva of black flies [28]), and selectively suppressing Th1-type cytokine responses but not Th2-type responses [21,27,29]. A Th2-polarization of immune responses has been reported not only for mosquito [29], but also tick saliva [30,31]. Another mechanism by which mosquito salivary proteins hamper adaptive immune responses is through the inhibition of macrophage phagocytosis and by interfering with the ability of these cells to present antigen by decreasing MHC class I and class II expression (Donald Champagne, unpublished observation).…”