Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes.
Visceral Leishmaniasis is a chronic zoonosis and, if left untreated, can be fatal. Infected dogs have decreased cellular immunity (Th1) and develop a potent humoral response (Th2), which is not effective for elimination of the protozoan. Immune response can be modulated by microRNAs (miRNAs), howeve...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0226192 |
| _version_ | 1819110887259111424 |
|---|---|
| author | Larissa Martins Melo Jaqueline Poleto Bragato Gabriela Lovizutto Venturin Gabriela Torres Rebech Sidnei Ferro Costa Leandro Encarnação Garcia Flávia Lombardi Lopes Flávia de Rezende Eugênio Paulo Sérgio Patto Dos Santos Valéria Marçal Felix de Lima |
| author_facet | Larissa Martins Melo Jaqueline Poleto Bragato Gabriela Lovizutto Venturin Gabriela Torres Rebech Sidnei Ferro Costa Leandro Encarnação Garcia Flávia Lombardi Lopes Flávia de Rezende Eugênio Paulo Sérgio Patto Dos Santos Valéria Marçal Felix de Lima |
| author_sort | Larissa Martins Melo |
| collection | DOAJ |
| description | Visceral Leishmaniasis is a chronic zoonosis and, if left untreated, can be fatal. Infected dogs have decreased cellular immunity (Th1) and develop a potent humoral response (Th2), which is not effective for elimination of the protozoan. Immune response can be modulated by microRNAs (miRNAs), however, characterization of miRNAs and their possible regulatory role in the spleen of infected dogs have not been done. We evaluated miRNA expression in splenic leukocytes (SL) from dogs naturally infected with Leishmania infantum and developing leishmaniasis (CanL; n = 8) compared to healthy dogs (n = 4). Microarray analysis showed increased expression of miR 21, miR 148a, miR 7 and miR 615, and downregulation of miR 150, miR 125a and miR 125b. Real-time PCR validated the differential expression of miR 21, miR 148a and miR 615. Further, decrease of miR 21 in SL, by means of transfection with a miR 21 inhibitor, increased the IL-12 cytokine and the T-bet/GATA-3 ratio, and decreased parasite load on SL of dogs with CanL. Taken together, these findings suggest that L. infantum infection alters splenic expression of miRNAs and that miR 21 interferes in the cellular immune response of L. infantum-infected dogs, placing this miRNA as a possible therapeutic target in CanL. |
| first_indexed | 2024-12-22T03:48:51Z |
| format | Article |
| id | doaj.art-7be52e149fd94ebfadc41b8338c49e88 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T03:48:51Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7be52e149fd94ebfadc41b8338c49e882022-12-21T18:40:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011412e022619210.1371/journal.pone.0226192Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes.Larissa Martins MeloJaqueline Poleto BragatoGabriela Lovizutto VenturinGabriela Torres RebechSidnei Ferro CostaLeandro Encarnação GarciaFlávia Lombardi LopesFlávia de Rezende EugênioPaulo Sérgio Patto Dos SantosValéria Marçal Felix de LimaVisceral Leishmaniasis is a chronic zoonosis and, if left untreated, can be fatal. Infected dogs have decreased cellular immunity (Th1) and develop a potent humoral response (Th2), which is not effective for elimination of the protozoan. Immune response can be modulated by microRNAs (miRNAs), however, characterization of miRNAs and their possible regulatory role in the spleen of infected dogs have not been done. We evaluated miRNA expression in splenic leukocytes (SL) from dogs naturally infected with Leishmania infantum and developing leishmaniasis (CanL; n = 8) compared to healthy dogs (n = 4). Microarray analysis showed increased expression of miR 21, miR 148a, miR 7 and miR 615, and downregulation of miR 150, miR 125a and miR 125b. Real-time PCR validated the differential expression of miR 21, miR 148a and miR 615. Further, decrease of miR 21 in SL, by means of transfection with a miR 21 inhibitor, increased the IL-12 cytokine and the T-bet/GATA-3 ratio, and decreased parasite load on SL of dogs with CanL. Taken together, these findings suggest that L. infantum infection alters splenic expression of miRNAs and that miR 21 interferes in the cellular immune response of L. infantum-infected dogs, placing this miRNA as a possible therapeutic target in CanL.https://doi.org/10.1371/journal.pone.0226192 |
| spellingShingle | Larissa Martins Melo Jaqueline Poleto Bragato Gabriela Lovizutto Venturin Gabriela Torres Rebech Sidnei Ferro Costa Leandro Encarnação Garcia Flávia Lombardi Lopes Flávia de Rezende Eugênio Paulo Sérgio Patto Dos Santos Valéria Marçal Felix de Lima Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. PLoS ONE |
| title | Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. |
| title_full | Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. |
| title_fullStr | Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. |
| title_full_unstemmed | Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. |
| title_short | Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. |
| title_sort | induction of mir 21 impairs the anti leishmania response through inhibition of il 12 in canine splenic leukocytes |
| url | https://doi.org/10.1371/journal.pone.0226192 |
| work_keys_str_mv | AT larissamartinsmelo inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT jaquelinepoletobragato inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT gabrielalovizuttoventurin inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT gabrielatorresrebech inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT sidneiferrocosta inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT leandroencarnacaogarcia inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT flavialombardilopes inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT flaviaderezendeeugenio inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT paulosergiopattodossantos inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes AT valeriamarcalfelixdelima inductionofmir21impairstheantileishmaniaresponsethroughinhibitionofil12incaninesplenicleukocytes |