The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties.
The pivotal role of spleen CD4(+) T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-con...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3141041?pdf=render |
| _version_ | 1818587281070489600 |
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| author | Sandra Marcia Muxel Ana Paula Freitas do Rosário Cláudia Augusta Zago Sheyla Inés Castillo-Méndez Luiz Roberto Sardinha Sérgio Marcelo Rodriguez-Málaga Niels Olsen Saraiva Câmara José Maria Álvarez Maria Regina D'Império Lima |
| author_facet | Sandra Marcia Muxel Ana Paula Freitas do Rosário Cláudia Augusta Zago Sheyla Inés Castillo-Méndez Luiz Roberto Sardinha Sérgio Marcelo Rodriguez-Málaga Niels Olsen Saraiva Câmara José Maria Álvarez Maria Regina D'Império Lima |
| author_sort | Sandra Marcia Muxel |
| collection | DOAJ |
| description | The pivotal role of spleen CD4(+) T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-conventional and conventional splenic CD4(+) T cells during P. chabaudi malaria. We took advantage of the fact that a great proportion of CD4(+) T cells generated in CD1d(-/-) mice are I-A(b)-restricted (conventional cells), while their counterparts in I-A(b-/-) mice are restricted by CD1d and other class IB major histocompatibility complex (MHC) molecules (non-conventional cells). We found that conventional CD4(+) T cells are the main protagonists of the immune response to infection, which develops in two consecutive phases concomitant with acute and chronic parasitaemias. The early phase of the conventional CD4(+) T cell response is intense and short lasting, rapidly providing large amounts of proinflammatory cytokines and helping follicular and marginal zone B cells to secrete polyclonal immunoglobulin. Both TNF-α and IFN-γ production depend mostly on conventional CD4(+) T cells. IFN-γ is produced simultaneously by non-conventional and conventional CD4(+) T cells. The early phase of the response finishes after a week of infection, with the elimination of a large proportion of CD4(+) T cells, which then gives opportunity to the development of acquired immunity. Unexpectedly, the major contribution of CD1d-restricted CD4(+) T cells occurs at the beginning of the second phase of the response, but not earlier, helping both IFN-γ and parasite-specific antibody production. We concluded that conventional CD4(+) T cells have a central role from the onset of P. chabaudi malaria, acting in parallel with non-conventional CD4(+) T cells as a link between innate and acquired immunity. This study contributes to the understanding of malaria immunology and opens a perspective for future studies designed to decipher the molecular mechanisms behind immune responses to Plasmodium infection. |
| first_indexed | 2024-12-16T09:06:22Z |
| format | Article |
| id | doaj.art-c347ee6681264e3d83c62c6c8d0c5bd7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:06:22Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c347ee6681264e3d83c62c6c8d0c5bd72022-12-21T22:37:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2243410.1371/journal.pone.0022434The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties.Sandra Marcia MuxelAna Paula Freitas do RosárioCláudia Augusta ZagoSheyla Inés Castillo-MéndezLuiz Roberto SardinhaSérgio Marcelo Rodriguez-MálagaNiels Olsen Saraiva CâmaraJosé Maria ÁlvarezMaria Regina D'Império LimaThe pivotal role of spleen CD4(+) T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-conventional and conventional splenic CD4(+) T cells during P. chabaudi malaria. We took advantage of the fact that a great proportion of CD4(+) T cells generated in CD1d(-/-) mice are I-A(b)-restricted (conventional cells), while their counterparts in I-A(b-/-) mice are restricted by CD1d and other class IB major histocompatibility complex (MHC) molecules (non-conventional cells). We found that conventional CD4(+) T cells are the main protagonists of the immune response to infection, which develops in two consecutive phases concomitant with acute and chronic parasitaemias. The early phase of the conventional CD4(+) T cell response is intense and short lasting, rapidly providing large amounts of proinflammatory cytokines and helping follicular and marginal zone B cells to secrete polyclonal immunoglobulin. Both TNF-α and IFN-γ production depend mostly on conventional CD4(+) T cells. IFN-γ is produced simultaneously by non-conventional and conventional CD4(+) T cells. The early phase of the response finishes after a week of infection, with the elimination of a large proportion of CD4(+) T cells, which then gives opportunity to the development of acquired immunity. Unexpectedly, the major contribution of CD1d-restricted CD4(+) T cells occurs at the beginning of the second phase of the response, but not earlier, helping both IFN-γ and parasite-specific antibody production. We concluded that conventional CD4(+) T cells have a central role from the onset of P. chabaudi malaria, acting in parallel with non-conventional CD4(+) T cells as a link between innate and acquired immunity. This study contributes to the understanding of malaria immunology and opens a perspective for future studies designed to decipher the molecular mechanisms behind immune responses to Plasmodium infection.http://europepmc.org/articles/PMC3141041?pdf=render |
| spellingShingle | Sandra Marcia Muxel Ana Paula Freitas do Rosário Cláudia Augusta Zago Sheyla Inés Castillo-Méndez Luiz Roberto Sardinha Sérgio Marcelo Rodriguez-Málaga Niels Olsen Saraiva Câmara José Maria Álvarez Maria Regina D'Império Lima The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PLoS ONE |
| title | The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. |
| title_full | The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. |
| title_fullStr | The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. |
| title_full_unstemmed | The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. |
| title_short | The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. |
| title_sort | spleen cd4 t cell response to blood stage plasmodium chabaudi malaria develops in two phases characterized by different properties |
| url | http://europepmc.org/articles/PMC3141041?pdf=render |
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