Anti-complement activity in the saliva of phlebotomine sand flies and other haematophagous insects

Abstract

The saliva of haematophagous insects has a series of pharmacological activities which may favour blood feeding. In the present study, an inhibitory effect on the complement system was observed in salivary extracts obtained from the phlebotomine sand flies Lutzomyia longipalpis and Lu. migonei. Saliva from Lu. longipalpis was capable of inhibiting both the classical and alternative pathways, while that from Lu. migonei acted only on the former. Other haematophagous insect species were screened for inhibition of the classical pathway. The triatomine bugs Panstrongylus megistus, Triatoma brasiliensis and Rhodnius prolixus were also able to inhibit the classical pathway whereas the mosquito Aedes aegyti and flea Ctenocephalides felis were not. The activity of Lu. longipalpis saliva on the classical pathway was partially characterized. The inhibitor is a protein of Mr 10000-30000 Da, which is very resistant to denaturation by heat. The inhibition of the complement system by phlebotomine sand flies may have a role in the transmission of Leishmania to the vertebrate hosts. The inhibitor molecule is thus a promising component of a vaccine to target salivary immunomodulators.

Identification of the most abundant secreted proteins from the salivary glands of the sand flyLutzomyia longipalpis, vector ofLeishmania chagasi

“…Anticomplement activity in Lu. longipalpis has been recently described (Cavalcante et al, 2003); because of its putative anti-protease activity, this cDNA may code for the salivary anti-complement activity.…”

Sand fly saliva: effects on host immune response and Leishmania transmission

“…The inhibitory molecule of the classical pathway present in the saliva of L. longipalpis is a heatstable protein of 10-30 kDa (Cavalcante et al 2003). Many components of the complement system are serine proteases (Klein and Hořejší 1997), therefore the molecule with anti-complement activity could be a serine protease inhibitor recently found in the cDNA library of L. longipalpis saliva ).…”

“…Anti-L. longipalpis saliva antibodies have been shown to partially inactivate the complement inhibitor (Cavalcante et al 2003) and completely abrogate the effect of L. longipalpis saliva on cytokine production by LPS-stimulated human monocytes (Costa et al 2004). Moreover, antimaxadilan antibodies decrease vasodilatory function of maxadilan in sensitized mice, which subsequently reduces blood meal acquisition and egg production of L. longipalpis (Milleron et al 2004b).…”

“…Recently, the most abundant secreted proteins have been identified also from the salivary glands of P. ariasi, P. argentipes and P. perniciosus (Anderson et al 2006. Sand fly species differ in protein composition (Volf et al 2000, Anderson et al 2006 as well as in pharmacological activities of saliva (Warburg et al 1994, Černá et al 2002, Cavalcante et al 2003; this may influence the protective effect on the progress of Leishmania infection. We have shown that antigens in sand fly saliva are species-specific Rohoušová 2001, Rohoušová et al 2005b) and, what is even more important, the protective effect is specific as well (Thiakaki et al 2005).…”

Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System

“…19 On the other hand, salivary gland extracts from hematophagous insects such as Lutzomyia longipalpis, Lutzomyia migonei, Panstrongylus megistus, Triatoma brasiliensis, and Rhodnius prolixus inhibit the complement system, thus favoring the feeding process. 20 Moreover, it has been probed that T. brasiliensis forced to ingest serum in conditions in which the protection of midgut by salivary inhibitors is bypassed, and showed damage by complement in the anterior midgut epithelium and cell death. 12 To address the role of salivary CRT on the hematophagous feeding process, we have cloned and characterized TiCRT and its S domain (TiS).…”