Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice.
Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. S...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-07-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009639&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850143460548411392 |
|---|---|
| author | Thaís Leal-Silva Flaviane Vieira-Santos Fabrício Marcus Silva Oliveira Luiza de Lima Silva Padrão Lucas Kraemer Pablo Hemanoel da Paixão Matias Camila de Almeida Lopes Ana Cristina Loiola Ruas Isabella Carvalho de Azevedo Denise Silva Nogueira Milene Alvarenga Rachid Marcelo Vidigal Caliari Remo Castro Russo Ricardo Toshio Fujiwara Lilian Lacerda Bueno |
| author_facet | Thaís Leal-Silva Flaviane Vieira-Santos Fabrício Marcus Silva Oliveira Luiza de Lima Silva Padrão Lucas Kraemer Pablo Hemanoel da Paixão Matias Camila de Almeida Lopes Ana Cristina Loiola Ruas Isabella Carvalho de Azevedo Denise Silva Nogueira Milene Alvarenga Rachid Marcelo Vidigal Caliari Remo Castro Russo Ricardo Toshio Fujiwara Lilian Lacerda Bueno |
| author_sort | Thaís Leal-Silva |
| collection | DOAJ |
| description | Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury. |
| format | Article |
| id | doaj-art-88e2d6f11a974743b2fbd9891049e4bf |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-88e2d6f11a974743b2fbd9891049e4bf2025-08-20T02:28:41ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352021-07-01157e000963910.1371/journal.pntd.0009639Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice.Thaís Leal-SilvaFlaviane Vieira-SantosFabrício Marcus Silva OliveiraLuiza de Lima Silva PadrãoLucas KraemerPablo Hemanoel da Paixão MatiasCamila de Almeida LopesAna Cristina Loiola RuasIsabella Carvalho de AzevedoDenise Silva NogueiraMilene Alvarenga RachidMarcelo Vidigal CaliariRemo Castro RussoRicardo Toshio FujiwaraLilian Lacerda BuenoToxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009639&type=printable |
| spellingShingle | Thaís Leal-Silva Flaviane Vieira-Santos Fabrício Marcus Silva Oliveira Luiza de Lima Silva Padrão Lucas Kraemer Pablo Hemanoel da Paixão Matias Camila de Almeida Lopes Ana Cristina Loiola Ruas Isabella Carvalho de Azevedo Denise Silva Nogueira Milene Alvarenga Rachid Marcelo Vidigal Caliari Remo Castro Russo Ricardo Toshio Fujiwara Lilian Lacerda Bueno Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. PLoS Neglected Tropical Diseases |
| title | Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. |
| title_full | Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. |
| title_fullStr | Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. |
| title_full_unstemmed | Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. |
| title_short | Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. |
| title_sort | detrimental role of il 33 st2 pathway sustaining a chronic eosinophil dependent th2 inflammatory response tissue damage and parasite burden during toxocara canis infection in mice |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009639&type=printable |
| work_keys_str_mv | AT thaislealsilva detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT flavianevieirasantos detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT fabriciomarcussilvaoliveira detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT luizadelimasilvapadrao detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT lucaskraemer detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT pablohemanoeldapaixaomatias detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT camiladealmeidalopes detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT anacristinaloiolaruas detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT isabellacarvalhodeazevedo detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT denisesilvanogueira detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT milenealvarengarachid detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT marcelovidigalcaliari detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT remocastrorusso detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT ricardotoshiofujiwara detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice AT lilianlacerdabueno detrimentalroleofil33st2pathwaysustainingachroniceosinophildependentth2inflammatoryresponsetissuedamageandparasiteburdenduringtoxocaracanisinfectioninmice |