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

Cytokine expression in lymph node cells from hamsters immunized with Lu. longipalpis followed by L. braziliensis infection.Hamsters (7 per group total) were inoculated three times in the right ear with Lu. longipalpis SGS (closed symbols) or with saline (open symbols) and were challenged in the left ear with 105 L. braziliensis in the presence of Lu. intermedia (squares) or Lu. longipalpis SGS (circles). The IFN-γ (A), IL-10 (B) and TGF-β (C) relative mRNA expression was evaluated by Real-Time PCR, 5 weeks after the infection. Points represent each animal, experiments were repeated five times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **<0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3104964&req=5

pntd-0001169-g003: Cytokine expression in lymph node cells from hamsters immunized with Lu. longipalpis followed by L. braziliensis infection.Hamsters (7 per group total) were inoculated three times in the right ear with Lu. longipalpis SGS (closed symbols) or with saline (open symbols) and were challenged in the left ear with 105 L. braziliensis in the presence of Lu. intermedia (squares) or Lu. longipalpis SGS (circles). The IFN-γ (A), IL-10 (B) and TGF-β (C) relative mRNA expression was evaluated by Real-Time PCR, 5 weeks after the infection. Points represent each animal, experiments were repeated five times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **<0.01.

Mentions: We studied the cytokine profile of immunized and infected hamsters three, five and eight weeks post challenge by real time PCR. At five weeks post-infection, IFN-γ levels were similar among all groups (Fig. 3A). Similar results were observed at all time points studied (Fig. S2A and D). There was a significant reduction in IL-10 expression (p = 0.026) in hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis plus Lu. intermedia SGS (Fig. 3B) compared to control unimmunized group. A significant reduction was also observed at three (p = 0.021) and eight (p = 0.043) weeks post infection (Fig. S2B and E). We also observed a significant reduction in the expression of TGF-β (p = 0.030) in hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis + Lu. intermedia SGS as compared to unimmunized control group (Fig. 3C). Similar results were obtained at 3 weeks post-infection (p = 0.040, Fig. S2C). However, the group of hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis plus Lu. longipalpis SGS showed significant reduction in TGF-β expression only at three weeks after infection (p = 0.050, Fig. S2C). We also analyzed the ratio IFN-γ/TGF-β and there were not significant differences between the immunized and non-immunized groups (data not shown).


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)

Cytokine expression in lymph node cells from hamsters immunized with Lu. longipalpis followed by L. braziliensis infection.Hamsters (7 per group total) were inoculated three times in the right ear with Lu. longipalpis SGS (closed symbols) or with saline (open symbols) and were challenged in the left ear with 105 L. braziliensis in the presence of Lu. intermedia (squares) or Lu. longipalpis SGS (circles). The IFN-γ (A), IL-10 (B) and TGF-β (C) relative mRNA expression was evaluated by Real-Time PCR, 5 weeks after the infection. Points represent each animal, experiments were repeated five times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0001169-g003: Cytokine expression in lymph node cells from hamsters immunized with Lu. longipalpis followed by L. braziliensis infection.Hamsters (7 per group total) were inoculated three times in the right ear with Lu. longipalpis SGS (closed symbols) or with saline (open symbols) and were challenged in the left ear with 105 L. braziliensis in the presence of Lu. intermedia (squares) or Lu. longipalpis SGS (circles). The IFN-γ (A), IL-10 (B) and TGF-β (C) relative mRNA expression was evaluated by Real-Time PCR, 5 weeks after the infection. Points represent each animal, experiments were repeated five times and were evaluated by Mann-Whitney non-parametric t test. *p<0.05; **<0.01.
Mentions: We studied the cytokine profile of immunized and infected hamsters three, five and eight weeks post challenge by real time PCR. At five weeks post-infection, IFN-γ levels were similar among all groups (Fig. 3A). Similar results were observed at all time points studied (Fig. S2A and D). There was a significant reduction in IL-10 expression (p = 0.026) in hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis plus Lu. intermedia SGS (Fig. 3B) compared to control unimmunized group. A significant reduction was also observed at three (p = 0.021) and eight (p = 0.043) weeks post infection (Fig. S2B and E). We also observed a significant reduction in the expression of TGF-β (p = 0.030) in hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis + Lu. intermedia SGS as compared to unimmunized control group (Fig. 3C). Similar results were obtained at 3 weeks post-infection (p = 0.040, Fig. S2C). However, the group of hamsters immunized with Lu. longipalpis SGS and challenged with L. braziliensis plus Lu. longipalpis SGS showed significant reduction in TGF-β expression only at three weeks after infection (p = 0.050, Fig. S2C). We also analyzed the ratio IFN-γ/TGF-β and there were not significant differences between the immunized and non-immunized groups (data not shown).

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