Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

Abstract

Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the African continent. These blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. Here we demonstrate that tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection. This effect was associated with a reduced inflammatory reaction at the site of infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12 mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not suppressed. We propose that tsetse fly saliva accelerates the onset of trypanosome infection by inhibiting local and systemic inflammatory responses involved in parasite control.African trypanosomes are extracellular protozoan flagellates that infect a broad range of vertebrate hosts, including humans, and rely for their transmission on tsetse flies (Glossina sp.), which are obligately blood-feeding organisms (62). In the mammalian host, the parasites establish controlled growth to ensure survival and optimal transmission. In order to escape the adaptive immune system, trypanosomes undergo antigenic variation by altering their major surface antigen, the variantspecific surface glycoprotein (VSG) (6). Beside this immune evasion mechanism, trypanosomes have been shown to modulate immune functions of macrophages (8, 43), T lymphocytes (56), and B lymphocytes (2). The main host immune effectors involved in parasite control are considered to be trypanosomespecific antibodies (30) and the cytokine tumor necrosis factor (TNF) (33). Concerning trypanosome-specific antibodies, increased VSG-reactive immunoglobulin M (IgM) and IgG2a antibody isotypes have been associated with improved control of trypanosome infections (34, 55). TNF, as a host cytokine, was released from activated macrophages in response to stimulation by soluble VSG (sVSG) and membrane-bound VSG (11,35). TNF was demonstrated to have trypanocidal properties for certain trypanosome stocks and to be associated with the occurrence of immune pathology in infected animals (33). As such, direct or indirect modulation of parasite-specific antibody induction and TNF release might influence trypanosome growth and the severity of infection.Focusing on the early stage of trypanosome infection in the mammalian host, the effect of tsetse fly salivary components on parasitemia onset and on the involved host antiparasite immune effectors has been poorly investigated. Studies with other blood-sucking arthropods, such as ticks and sand flies, have demonstrated that salivary proteins are potent modulators of host innate and adaptive immune responses. Especially for ticks, which are characterized by their extended feeding time, a broad repertoire of immune modulatory activities has been...

The Glossina morsitans tsetse fly saliva: General characteristics and identification of novel salivary proteins

“…Moreover, as is the case in many other blood-feeding arthropods (Ribeiro, 1995;Ribeiro and Francischetti, 2003), tsetse flies must have evolved a sophisticated array of salivary components to overcome host hemostatic responses. In addition, tsetse saliva has been reported to bias the host immune response towards antiinflammation (Caljon et al, 2006a) and to accelerate the onset of a T. brucei infection (Caljon et al, 2006b). However, molecular information on the individual tsetse salivary proteins and their biological activity remains scanty.…”

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

“…There was no discernible pattern in Th1 cytokine response following subsequent infestations. Reports of Th1 responses to ectoparasite feeding have been shown to be highly variable (Zeidner et al 1999;Hajnická et al 2001;Pechová et al 2004;Caljon et al 2006;Donovan et al 2007). Skin at the D. gallinae feeding site was not sampled, but the investigation of mRNA expression in skin would be interesting to determine if D. gallinae feeding stimulates local inflammatory responses such as those reported for ticks (Franzin et al 2009).…”

Identification of a functional Antigen5-related allergen in the saliva of a blood feeding insect, the tsetse fly

“…We have previously shown that immunization against saliva by repeated tsetse fly bites enhances the early onset of a trypanosome infection, suggesting that the parasite benefits from local hypersensitivity reactions for host colonisation (Caljon et al, 2006b).…”

“…are obligate blood feeding Diptera and the main vectors for human and veterinary parasitic diseases known as African trypanosomiasis. During each blood feeding event, they deposit a complex salivary mixture at the bite site that modulates the host immune system (Caljon et al, 2006a) and supports efficient parasite transmission (Caljon et al, 2006b). Repetitive exposure of hosts to stinging as well as biting insects might result in hypersensitivity reactions as a consequence of specific humoral and cellular immune responses.…”