Limits...
Lutzomyia longipalpis saliva or salivary protein LJM19 protects against Leishmania braziliensis and the saliva of its vector, Lutzomyia intermedia.

Tavares NM, Silva RA, Costa DJ, Pitombo MA, Fukutani KF, Miranda JC, Valenzuela JG, Barral A, de Oliveira CI, Barral-Netto M, Brodskyn C - PLoS Negl Trop Dis (2011)

Bottom Line: Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes.These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β.These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector.

View Article: PubMed Central - PubMed

Affiliation: Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.

ABSTRACT

Background: Leishmania transmission occurs in the presence of insect saliva. Immunity to Phlebotomus papatasi or Lutzomyia longipalpis saliva or salivary components confers protection against an infection by Leishmania in the presence of the homologous saliva. However, immunization with Lutzomyia intermedia saliva did not protect mice against Leishmania braziliensis plus Lu. intermedia saliva. In the present study, we have studied whether the immunization with Lu. longipalpis saliva or a DNA plasmid coding for LJM19 salivary protein would be protective against L. braziliensis infection in the presence of Lu. intermedia saliva, the natural vector for L. braziliensis.

Methodology/principal findings: Immunization with Lu. longipalpis saliva or with LJM19 DNA plasmid induced a Delayed-Type Hypersensitivity (DTH) response against Lu. longipalpis as well as against a Lu. intermedia saliva challenge. Immunized and unimmunized control hamsters were then intradermally infected in the ears with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia saliva. Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes. These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β. Animals immunized with LJM19 DNA plasmid presented similar findings in protection and immune response and additionally increased IFN-γ expression.

Conclusions/significance: Immunization with Lu. longipalpis saliva or with a DNA plasmid coding LJM19 salivary protein induced protection in hamsters challenged with L. braziliensis plus Lu. intermedia saliva. These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector.

Show MeSH

Related in: MedlinePlus

Ear thickness and parasite load in LJM19 immunized hamsters following infection with L. braziliensis.Hamsters (12 per group total) were inoculated three times in the right ear with DNA plasmid coding LJM19 salivary protein (closed triangle) or empty DNA plasmid (CTR - open triangle) and were challenged intradermally in the left ear with 105 L. braziliensis stationary promastigotes in the presence of Lu. intermedia SGS. The course of lesion development was monitored weekly and points represent the means and standard errors of the means (A). The areas contained underneath the curves (AUC) obtained in A for each group was compared (B). Five weeks after the infection, the parasite load was evaluated in the ear (C) and draining lymph node (D) by LDA, estimated by ELIDA. Experiments were repeated three times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **p<0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3104964&req=5

pntd-0001169-g004: Ear thickness and parasite load in LJM19 immunized hamsters following infection with L. braziliensis.Hamsters (12 per group total) were inoculated three times in the right ear with DNA plasmid coding LJM19 salivary protein (closed triangle) or empty DNA plasmid (CTR - open triangle) and were challenged intradermally in the left ear with 105 L. braziliensis stationary promastigotes in the presence of Lu. intermedia SGS. The course of lesion development was monitored weekly and points represent the means and standard errors of the means (A). The areas contained underneath the curves (AUC) obtained in A for each group was compared (B). Five weeks after the infection, the parasite load was evaluated in the ear (C) and draining lymph node (D) by LDA, estimated by ELIDA. Experiments were repeated three times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **p<0.01.

Mentions: We recently showed that immunization with a DNA plasmid coding for the salivary protein LJM19, one of the most abundant secreted proteins in Lu. longipalpis saliva, protected hamsters against visceral leishmaniasis [9]. Since Lu. longipalpis SGS protect hamsters against an infection with L. braziliensis (Fig. 2), we tested if immunizations with LJM19 DNA plasmid could also protect against L. braziliensis infection. This hypothesis is based on the fact that immunization with LJM19 DNA plasmid also induced a DTH response against Lu. intermedia SGS (Fig. 1D). Hamsters immunized with LJM19 DNA plasmid were challenged with L. braziliensis + Lu. intermedia SGS. As shown in Fig. 4A, the onset of lesion development is at three weeks post infection in both groups: LJM19 DNA plasmid immunized and empty DNA plasmid control. At four weeks, the ear thickness in immunized hamsters peaked around 1.0 mm and is maintained without alterations. In control group, the ear thickness increased up to 1.5 mm until eight weeks post infection (Fig. 4A). Importantly, a significant reduction (p = 0.038) in disease burden was observed in immunized compared to control group (Fig. 4B).


Lutzomyia longipalpis saliva or salivary protein LJM19 protects against Leishmania braziliensis and the saliva of its vector, Lutzomyia intermedia.

Tavares NM, Silva RA, Costa DJ, Pitombo MA, Fukutani KF, Miranda JC, Valenzuela JG, Barral A, de Oliveira CI, Barral-Netto M, Brodskyn C - PLoS Negl Trop Dis (2011)

Ear thickness and parasite load in LJM19 immunized hamsters following infection with L. braziliensis.Hamsters (12 per group total) were inoculated three times in the right ear with DNA plasmid coding LJM19 salivary protein (closed triangle) or empty DNA plasmid (CTR - open triangle) and were challenged intradermally in the left ear with 105 L. braziliensis stationary promastigotes in the presence of Lu. intermedia SGS. The course of lesion development was monitored weekly and points represent the means and standard errors of the means (A). The areas contained underneath the curves (AUC) obtained in A for each group was compared (B). Five weeks after the infection, the parasite load was evaluated in the ear (C) and draining lymph node (D) by LDA, estimated by ELIDA. Experiments were repeated three times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104964&req=5

pntd-0001169-g004: Ear thickness and parasite load in LJM19 immunized hamsters following infection with L. braziliensis.Hamsters (12 per group total) were inoculated three times in the right ear with DNA plasmid coding LJM19 salivary protein (closed triangle) or empty DNA plasmid (CTR - open triangle) and were challenged intradermally in the left ear with 105 L. braziliensis stationary promastigotes in the presence of Lu. intermedia SGS. The course of lesion development was monitored weekly and points represent the means and standard errors of the means (A). The areas contained underneath the curves (AUC) obtained in A for each group was compared (B). Five weeks after the infection, the parasite load was evaluated in the ear (C) and draining lymph node (D) by LDA, estimated by ELIDA. Experiments were repeated three times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **p<0.01.
Mentions: We recently showed that immunization with a DNA plasmid coding for the salivary protein LJM19, one of the most abundant secreted proteins in Lu. longipalpis saliva, protected hamsters against visceral leishmaniasis [9]. Since Lu. longipalpis SGS protect hamsters against an infection with L. braziliensis (Fig. 2), we tested if immunizations with LJM19 DNA plasmid could also protect against L. braziliensis infection. This hypothesis is based on the fact that immunization with LJM19 DNA plasmid also induced a DTH response against Lu. intermedia SGS (Fig. 1D). Hamsters immunized with LJM19 DNA plasmid were challenged with L. braziliensis + Lu. intermedia SGS. As shown in Fig. 4A, the onset of lesion development is at three weeks post infection in both groups: LJM19 DNA plasmid immunized and empty DNA plasmid control. At four weeks, the ear thickness in immunized hamsters peaked around 1.0 mm and is maintained without alterations. In control group, the ear thickness increased up to 1.5 mm until eight weeks post infection (Fig. 4A). Importantly, a significant reduction (p = 0.038) in disease burden was observed in immunized compared to control group (Fig. 4B).

Bottom Line: Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes.These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β.These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector.

View Article: PubMed Central - PubMed

Affiliation: Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.

ABSTRACT

Background: Leishmania transmission occurs in the presence of insect saliva. Immunity to Phlebotomus papatasi or Lutzomyia longipalpis saliva or salivary components confers protection against an infection by Leishmania in the presence of the homologous saliva. However, immunization with Lutzomyia intermedia saliva did not protect mice against Leishmania braziliensis plus Lu. intermedia saliva. In the present study, we have studied whether the immunization with Lu. longipalpis saliva or a DNA plasmid coding for LJM19 salivary protein would be protective against L. braziliensis infection in the presence of Lu. intermedia saliva, the natural vector for L. braziliensis.

Methodology/principal findings: Immunization with Lu. longipalpis saliva or with LJM19 DNA plasmid induced a Delayed-Type Hypersensitivity (DTH) response against Lu. longipalpis as well as against a Lu. intermedia saliva challenge. Immunized and unimmunized control hamsters were then intradermally infected in the ears with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia saliva. Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes. These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β. Animals immunized with LJM19 DNA plasmid presented similar findings in protection and immune response and additionally increased IFN-γ expression.

Conclusions/significance: Immunization with Lu. longipalpis saliva or with a DNA plasmid coding LJM19 salivary protein induced protection in hamsters challenged with L. braziliensis plus Lu. intermedia saliva. These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector.

Show MeSH
Related in: MedlinePlus