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HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda
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| Zeitschriftentitel: | Frontiers in Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , |
| In: | Frontiers in Immunology, 12, 2021 |
| Format: | E-Article |
| Sprache: | Unbestimmt |
| veröffentlicht: |
Frontiers Media SA
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| Schlagwörter: |
| author_facet |
Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. |
|---|---|
| author |
Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. |
| spellingShingle |
Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. Frontiers in Immunology HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda Immunology Immunology and Allergy |
| author_sort |
digitale, jean c. |
| spelling |
Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. 1664-3224 Frontiers Media SA Immunology Immunology and Allergy http://dx.doi.org/10.3389/fimmu.2021.650028 <jats:p>Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to <jats:italic>P. falciparum</jats:italic> malaria is unclear. Increasing evidence indicates that acquired immunity to <jats:italic>P. falciparum</jats:italic> is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by <jats:italic>P. falciparum</jats:italic>-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of <jats:italic>P. falciparum</jats:italic> infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B<jats:sup>*</jats:sup>53:01 and HLA-C<jats:sup>*</jats:sup>06:02, that were associated with a higher prevalence of <jats:italic>P. falciparum</jats:italic> infection. Notably, no class I or II HLA alleles were found to be associated with protection from <jats:italic>P. falciparum</jats:italic> parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in <jats:italic>P. falciparum</jats:italic> immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to <jats:italic>P. falciparum</jats:italic> at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the <jats:italic>P. falciparum</jats:italic> life cycle is warranted.</jats:p> HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda Frontiers in Immunology |
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| title |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_unstemmed |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_full |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_fullStr |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_full_unstemmed |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_short |
HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_sort |
hla alleles b*53:01 and c*06:02 are associated with higher risk of p. falciparum parasitemia in a cohort in uganda |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.3389/fimmu.2021.650028 |
| publishDate |
2021 |
| physical |
|
| description |
<jats:p>Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to <jats:italic>P. falciparum</jats:italic> malaria is unclear. Increasing evidence indicates that acquired immunity to <jats:italic>P. falciparum</jats:italic> is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by <jats:italic>P. falciparum</jats:italic>-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of <jats:italic>P. falciparum</jats:italic> infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B<jats:sup>*</jats:sup>53:01 and HLA-C<jats:sup>*</jats:sup>06:02, that were associated with a higher prevalence of <jats:italic>P. falciparum</jats:italic> infection. Notably, no class I or II HLA alleles were found to be associated with protection from <jats:italic>P. falciparum</jats:italic> parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in <jats:italic>P. falciparum</jats:italic> immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to <jats:italic>P. falciparum</jats:italic> at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the <jats:italic>P. falciparum</jats:italic> life cycle is warranted.</jats:p> |
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| author | Digitale, Jean C., Callaway, Perri C., Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, Feeney, Margaret E. |
| author_facet | Digitale, Jean C., Callaway, Perri C., Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, Feeney, Margaret E., Digitale, Jean C., Callaway, Perri C., Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, Feeney, Margaret E. |
| author_sort | digitale, jean c. |
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| description | <jats:p>Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to <jats:italic>P. falciparum</jats:italic> malaria is unclear. Increasing evidence indicates that acquired immunity to <jats:italic>P. falciparum</jats:italic> is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by <jats:italic>P. falciparum</jats:italic>-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of <jats:italic>P. falciparum</jats:italic> infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B<jats:sup>*</jats:sup>53:01 and HLA-C<jats:sup>*</jats:sup>06:02, that were associated with a higher prevalence of <jats:italic>P. falciparum</jats:italic> infection. Notably, no class I or II HLA alleles were found to be associated with protection from <jats:italic>P. falciparum</jats:italic> parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in <jats:italic>P. falciparum</jats:italic> immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to <jats:italic>P. falciparum</jats:italic> at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the <jats:italic>P. falciparum</jats:italic> life cycle is warranted.</jats:p> |
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| spelling | Digitale, Jean C. Callaway, Perri C. Martin, Maureen Nelson, George Viard, Mathias Rek, John Arinaitwe, Emmanuel Dorsey, Grant Kamya, Moses Carrington, Mary Rodriguez-Barraquer, Isabel Feeney, Margaret E. 1664-3224 Frontiers Media SA Immunology Immunology and Allergy http://dx.doi.org/10.3389/fimmu.2021.650028 <jats:p>Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to <jats:italic>P. falciparum</jats:italic> malaria is unclear. Increasing evidence indicates that acquired immunity to <jats:italic>P. falciparum</jats:italic> is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by <jats:italic>P. falciparum</jats:italic>-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of <jats:italic>P. falciparum</jats:italic> infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B<jats:sup>*</jats:sup>53:01 and HLA-C<jats:sup>*</jats:sup>06:02, that were associated with a higher prevalence of <jats:italic>P. falciparum</jats:italic> infection. Notably, no class I or II HLA alleles were found to be associated with protection from <jats:italic>P. falciparum</jats:italic> parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in <jats:italic>P. falciparum</jats:italic> immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to <jats:italic>P. falciparum</jats:italic> at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the <jats:italic>P. falciparum</jats:italic> life cycle is warranted.</jats:p> HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda Frontiers in Immunology |
| spellingShingle | Digitale, Jean C., Callaway, Perri C., Martin, Maureen, Nelson, George, Viard, Mathias, Rek, John, Arinaitwe, Emmanuel, Dorsey, Grant, Kamya, Moses, Carrington, Mary, Rodriguez-Barraquer, Isabel, Feeney, Margaret E., Frontiers in Immunology, HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda, Immunology, Immunology and Allergy |
| title | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_full | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_fullStr | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_full_unstemmed | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_short | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| title_sort | hla alleles b*53:01 and c*06:02 are associated with higher risk of p. falciparum parasitemia in a cohort in uganda |
| title_unstemmed | HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.3389/fimmu.2021.650028 |