Saliva from Lutzomyia longipalpis Induces CC Chemokine Ligand 2/Monocyte Chemoattractant Protein-1 Expression and Macrophage Recruitment

Abstract

Saliva of bloodfeeding arthropods has been incriminated in facilitating the establishment of parasite in their host. We report on the leukocyte chemoattractive effect of salivary gland homogenate (SGH) from Lutzomyia longipalpis on saliva-induced inflammation in an air pouch model. SGH (0.5 pair/animal) was inoculated in the air pouch formed in the back of BALB/c or C57BL/6 mice. L. longipalpis SGH induced a significant influx of macrophages in BALB/c but not in C57BL/6 mice. SGH-induced cell recruitment reached a peak at 12 h after inoculation and was higher than that induced by the LPS control. This differential cell recruitment in BALB/c mice was directly correlated to an increase in CCL2/MCP-1 expression in the air pouch lining tissue. In fact, treatment with bindarit, an inhibitor of CCL2/MCP-1 synthesis, and also with a specific anti-MCP-1 mAb resulted in drastic reduction of macrophage recruitment and inhibition of CCL2/MCP-1 expression in the lining tissue. CCL2/MCP-1 production was also seen in vitro when J774 murine macrophages were exposed to L. longipalpis SGH. The SGH effect was abrogated by preincubation with serum containing anti-SGH IgG Abs as well as in mice previously sensitized with L. longipalpis bites. Interestingly, the combination of SGH with Leishmania chagasi induced an increased recruitment of neutrophils and macrophages when compared with L. chagasi alone. Taken together these results suggest that SGH not only induces the recruitment of a greater number of macrophages by enhancing CCL2/MCP-1 production but also synergizes with L. chagasi to recruit more inflammatory cells to the site of inoculation.

Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

“…Lu. longipalpis saliva was implicated in increased MCP-1 expression and macrophage influx in a murine air pouch model [29]. In experiments performed in mice, saliva from Lu.…”

“…In experiments performed in mice, saliva from Lu. longipalpis has been shown to induce cell recruitment into the site of injection, differing in mice of diverse genetic background [29]. Induction of a DTH-like reaction by sand fly saliva is thought to be a survival strategy.…”

Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against trinitrobenzene sulfonic acid-induced colitis

“…In vivo, the compound has been shown to ameliorate joint damage in rat adjuvant arthritis [9], to limit glomerular injury and prolong survival of NZB/W lupus mice [10,11], and to protect mice against acute pancreatitis [12]. Several studies have demonstrated that bindarit is an inhibitor of MCP-1 production in vitro and in vivo and have suggested that its beneficial effects on animal models of inflammation are related to its anti-MCP-1 activity [8][9][10][11][12][13].…”

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

“…[23][24][25][26][27] With the application of the mouse air pouch model, genetic factors, including those encoding cytokines, proteinases and other enzymes, and adhesion molecules were identified in inflammation; the combination with spontaneous gene deficiencies or gene knockout technology further enhanced insights into inflammatory processes. [28][29][30][31][32][33] With the introduction of nanomedicines, the awareness of immunomodulating effects has increased but still remains problematic and challenging. Laboratories are collaborating worldwide to define, compare, and validate, not only toxicology tests, but also assays to measure effects of nanoparticles on immune responses.…”