Effects of Salivary Gland Homogenate from Wild‐Caught and Laboratory‐Reared <i>Lutzomyia longipalpis</i> on the Evolution and Immunomodulation of <i>Leishmania (Leishmania) amazonensis</i> Infection

Laurenti, Márcia Dalastra; Matta, Vânia Lúcia Ribeiro da; Pernichelli, Tadeu; Secundino, Nágila Francinete Costa; Pinto, Luciana Conceição; Corbett, Carlos Eduardo Pereira; Pimenta, P. P. F.

doi:10.1111/j.1365-3083.2009.02310.x

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…5 It was reported that colonized and wild-caught Lutzomyia longipalpis differ in the composition and the amount of salivary proteins and these differences may account for the lower effect observed on the modulation of experimental Leishmania infection by wild-caught SGH. 6,7 Thus, these studies provide good evidence that the outcome of Leishmania infection differs significantly between colonized and wild-caught salivary gland proteins. Our aim in this study was to assess the protective effect of pre-immunization with SGH of long-term colonized P. papatasi on experimental L. major challenge co-inoculated with SGH of wild-caught P. papatasi .…”

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confidence: 74%

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Ahmed¹,

Kaabi²,

Chelbi³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Several studies have shown that pre-immunization of mice with needle-injected saliva or pre-exposure to uninfected bites of Phlebotomus papatasi provided protection against infection with Leishmania major , the etiologic agent of zoonotic cutaneous leishmaniasis (ZCL).1-3 These studies were performed by using long-term laboratory colonized sand flies mainly because of the difficulty of working with wild-caught flies. A puzzling fact is that people in leishmaniasis-endemic areas succumb of ZCL despite the high frequency of uninfected bites compared with infected ones. 4 We showed in a previous study that pre-immunization of mice with salivary gland homogenate (SGH) of wild-caught P. papatasi does not confer protection against L. major co-inoculated with the same type of SGH compared with a significant protection obtained when pre-immunization and challenge were performed with SGH of long-term colonized flies. 5 It was reported that colonized and wild-caught Lutzomyia longipalpis differ in the composition and the amount of salivary proteins and these differences may account for the lower effect observed on the modulation of experimental Leishmania infection by wild-caught SGH. 6,7 Thus, these studies provide good evidence that the outcome of Leishmania infection differs significantly between colonized and wild-caught salivary gland proteins. Our aim in this study was to assess the protective effect of pre-immunization with SGH of long-term colonized P. papatasi on experimental L. major challenge co-inoculated with SGH of wild-caught P. papatasi .Phlebotomus papatasi (Tunisian strain that originated in the Governorate of Sidi Bouzid) have been reared at the Vector Ecology Laboratory of the Institut Pasteur de Tunis since 2003. 8 This colony is maintained without being supplemented periodically with wild-caught P. papatasi . Generation F 39 was used in this study. Wild sand flies were collected using CDC light traps from animal shelters located in the village of Felta (Governorate of Sidi Bouzid), a focus highly endemic for ZCL.9 Preparation of SGH from laboratory-reared and wild-caught P. papatasi was performed as described. 5 A highly virulent strain of L. major , MHOM/TN/95/GLC94, isolated from a patient in Tunisia was used in this study. 5 We used female BALB/c mice (6-8 weeks of age) bred in the animal facility of the Institut Pasteur de Tunis.Mice were immunized intradermally in the right ear with the equivalent of two pairs of salivary glands in 10 µL of phosphate-buffered saline (PBS). Two groups of 10 mice each were pre-immunized with SGH of long-term colonized female P. papatasi (F 39 ), once a week for two weeks. In the fourth week, the first [CSGH (F 39 )-L.m+CSGH (F 39 )] and the second [CSGH (F 39 )-L.m+WSGH] groups were challenged with 10 6 stationary phase L. major promastigotes in 50 µL of PBS co-inoculated subcutaneously in the right hind footpads with SGH of long-term, colonized and SGH of wild-caught, female P. papatasi , respectively. Three control groups of 10 mice each were used in this stud...

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mentioning

confidence: 74%

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Ahmed¹,

Kaabi²,

Chelbi³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…Therefore, these experiments may need to be repeated normalizing the amount of salivary proteins when using colonized vs. wild caught flies. In fact, Laurenti et al (2009a,b) showed that salivary proteins from field-captured L. longipalpis impacted the immune system differently from laboratory-reared sand flies. Nevertheless, this work clearly indicates (by SDS-PAGE analysis) that one salivary gland pair from wild caught sand flies had fewer amounts of proteins when compared to a salivary gland pair from colonized flies.…”

Section: Challenges For Vaccine Developmentmentioning

confidence: 99%

The Immune Response to Sand Fly Salivary Proteins and Its Influence on Leishmania Immunity

2012

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Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic. Immunization with a single salivary protein or exposure to uninfected bites was shown to result in a protective immune response against leishmaniasis. Antibodies to saliva were not required for this protection. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review the immunity to sand fly salivary proteins in the context of its vector–parasite–host combinations and their vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

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“…Among these factors, the infection-potentiating effect of sand fly salivary molecules [17], [18], [19], [20] has generated a great deal of excitement in the research community because: 1) it provides clues about immunobiological determinants of resistance or susceptibility to Leishmania infection and 2) it provides additional targets for vaccines to prevent leishmaniasis. Sand fly saliva plays an important role in the transmission of Leishmania parasites, facilitating their survival and dissemination in tissues of the vertebrate hosts by promoting a Th2-skewed immune response at the bite site [21], [22], [23]. Vaccines directed to sand fly saliva are expected to induce protective immunity by neutralizing the biological activity of salivary immuno-modulators and by generating a tissue microenvironment that promotes the destruction of parasites delivered, along with saliva, while sand flies take a blood meal [17], [24], [25].…”

Section: Introductionmentioning

confidence: 99%

BluePort: A Platform to Study the Eosinophilic Response of Mice to the Bite of a Vector of Leishmania Parasites, Lutzomyia longipalpis Sand Flies

et al. 2010

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BackgroundVisceral Leishmaniasis is a serious human disease transmitted, in the New World, by Lutzomyia longipalpis sand flies. Natural resistance to Leishmania transmission in residents of endemic areas has been attributed to the acquisition of immunity to sand fly salivary proteins. One theoretical way to accelerate the acquisition of this immunity is to increase the density of antigen-presenting cells at the sand fly bite site. Here we describe a novel tissue platform that can be used for this purpose.Methodology/Principal FindingsBluePort is a well-vascularized and macrophage-rich compartment induced in the subcutaneous tissue of mice via injection of agarose beads covered with Cibacron blue. We describe the sequence of inflammatory events leading to its formation and how it can be used to study the dermal response to the bite of L. longipalpis sand flies. Results presented indicate that a shift in the inflammatory response, from neutrophilic to eosinophilic, is the main histopathological feature associated with the immunity acquired through repeated exposure to the bite of sand flies, and that the BluePort tissue compartment could be used to accelerate this process. In addition, changes observed inside the BluePort parenchyma indicate that it could be used to study complex immunobiological processes, and to develop ectopic secondary lymphoid structures.Conclusions/SignificanceUnderstanding the characteristics of the dermal response to the bite of sand flies is a critical element of strategies to control leishmaniasis using vaccines that target salivary proteins. Finding that dermal eosinophilia is such a prominent component of the anti-salivary immunity induced by repeated exposure to sand fly bites raises one important consideration: how to avoid the immunological conflict derived from a protective Th2-driven immunity directed to sand fly saliva with a protective Th1-driven immunity directed to the parasite. The BluePort platform is an ideal tool to address experimentally this conundrum.

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Effects of Salivary Gland Homogenate from Wild‐Caught and Laboratory‐Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection

Cited by 23 publications

References 29 publications

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

The Immune Response to Sand Fly Salivary Proteins and Its Influence on Leishmania Immunity

BluePort: A Platform to Study the Eosinophilic Response of Mice to the Bite of a Vector of Leishmania Parasites, Lutzomyia longipalpis Sand Flies

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