Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages
IntroductionMacrophages play a crucial immunological role in maintaining pregnancy. Placental malaria infection may cause dysfunction in decidual macrophages which then culminates in the associated pregnancy complications. Here, we determined the influence of placental malaria on decidual macrophage...
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Frontiers Media S.A.
2025-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497936/full |
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| author | Fred Owino Fred Owino Fred Owino Caroline Kijogi Caroline Kijogi Caroline Kijogi Omu Anzala Omu Anzala Edwin Walong Obiero Jael Steven G. Nyanjom Agola Lelo Eric Bernard N. Kanoi Bernard N. Kanoi Jesse Gitaka Jesse Gitaka |
| author_facet | Fred Owino Fred Owino Fred Owino Caroline Kijogi Caroline Kijogi Caroline Kijogi Omu Anzala Omu Anzala Edwin Walong Obiero Jael Steven G. Nyanjom Agola Lelo Eric Bernard N. Kanoi Bernard N. Kanoi Jesse Gitaka Jesse Gitaka |
| author_sort | Fred Owino |
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| description | IntroductionMacrophages play a crucial immunological role in maintaining pregnancy. Placental malaria infection may cause dysfunction in decidual macrophages which then culminates in the associated pregnancy complications. Here, we determined the influence of placental malaria on decidual macrophages, by assessing their distribution based on their unique phenotypes, and examining their expression levels of transcription factors as well as angiogenic factors, in placentas from women living in a malaria-endemic area.MethodsWe compared these macrophage parameters in placentas from malaria infected women to those from the uninfected women. Placentas were collected upon delivery and malaria infection determined by histology together with PCR from dry blood spots obtained from placental blood. Following enzymatic dissociation of placental tissue, immune cells were enriched from the total population of placental cells by density centrifugation. Macrophage phenotypic characteristics were then analyzed from the placental immune cells by flow cytometry. The expression of surface markers CD68, CD80, CD86, CD163, CD206, and CD209, was used to delineate the macrophage populations. For gene expression profiling, macrophages were isolated from the placental immune cells and the expression level of transcription factors STAT-1, IRF-5, STAT-6, c-Maf and angiogenic factors ANG-1, ANG-2 and VEGF determined by qPCR.Results and DiscussionWe found no difference in the total macrophage populations and M1 and M2 macrophage profiles between uninfected and infected placentas, however, M2 macrophages were significantly higher compared to their M1 counterparts regardless of infection status. Notably, the gene expression levels of the transcription factor STAT-6 and angiogenic factor ANG-1 were significantly lower in infected placentas. These findings provide a basis for further understanding of the role of placental macrophages in placental malaria pathogenesis. Analysis of the functional consequences of these observations is needed to determine if these factors can be explored to reprogram macrophage polarization to desired state. |
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| id | doaj-art-97065778105a4c7fac34820e77389fc3 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-97065778105a4c7fac34820e77389fc32025-02-11T06:59:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14979361497936Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophagesFred Owino0Fred Owino1Fred Owino2Caroline Kijogi3Caroline Kijogi4Caroline Kijogi5Omu Anzala6Omu Anzala7Edwin Walong8Obiero Jael9Steven G. Nyanjom10Agola Lelo Eric11Bernard N. Kanoi12Bernard N. Kanoi13Jesse Gitaka14Jesse Gitaka15Biochemistry Department, Jomo Kenyatta University of Agriculture and Technology, Juja, KenyaCentre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Research in Infectious Diseases, Mount Kenya University, Thika, KenyaDepartment of Pharmacotherapy of Lifestyle-related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, JapanDepartment of Medical Microbiology, Kenya AIDS Vaccine Initiative (KAVI) Institute of Clinical Research, Nairobi, KenyaDepartment of Medical Microbiology, University of Nairobi, Nairobi, KenyaSchool of Medicine, Maseno University, Kisumu, KenyaReproductive Health and Biology, Kenya Institute of Primate Research, Nairobi, KenyaBiochemistry Department, Jomo Kenyatta University of Agriculture and Technology, Juja, KenyaCentre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Research in Infectious Diseases, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Research in Infectious Diseases, Mount Kenya University, Thika, KenyaIntroductionMacrophages play a crucial immunological role in maintaining pregnancy. Placental malaria infection may cause dysfunction in decidual macrophages which then culminates in the associated pregnancy complications. Here, we determined the influence of placental malaria on decidual macrophages, by assessing their distribution based on their unique phenotypes, and examining their expression levels of transcription factors as well as angiogenic factors, in placentas from women living in a malaria-endemic area.MethodsWe compared these macrophage parameters in placentas from malaria infected women to those from the uninfected women. Placentas were collected upon delivery and malaria infection determined by histology together with PCR from dry blood spots obtained from placental blood. Following enzymatic dissociation of placental tissue, immune cells were enriched from the total population of placental cells by density centrifugation. Macrophage phenotypic characteristics were then analyzed from the placental immune cells by flow cytometry. The expression of surface markers CD68, CD80, CD86, CD163, CD206, and CD209, was used to delineate the macrophage populations. For gene expression profiling, macrophages were isolated from the placental immune cells and the expression level of transcription factors STAT-1, IRF-5, STAT-6, c-Maf and angiogenic factors ANG-1, ANG-2 and VEGF determined by qPCR.Results and DiscussionWe found no difference in the total macrophage populations and M1 and M2 macrophage profiles between uninfected and infected placentas, however, M2 macrophages were significantly higher compared to their M1 counterparts regardless of infection status. Notably, the gene expression levels of the transcription factor STAT-6 and angiogenic factor ANG-1 were significantly lower in infected placentas. These findings provide a basis for further understanding of the role of placental macrophages in placental malaria pathogenesis. Analysis of the functional consequences of these observations is needed to determine if these factors can be explored to reprogram macrophage polarization to desired state.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497936/fullplacental malariamacrophagesM1/M2 macrophage polarizationtranscription factorsangiogenic factors |
| spellingShingle | Fred Owino Fred Owino Fred Owino Caroline Kijogi Caroline Kijogi Caroline Kijogi Omu Anzala Omu Anzala Edwin Walong Obiero Jael Steven G. Nyanjom Agola Lelo Eric Bernard N. Kanoi Bernard N. Kanoi Jesse Gitaka Jesse Gitaka Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages Frontiers in Immunology placental malaria macrophages M1/M2 macrophage polarization transcription factors angiogenic factors |
| title | Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages |
| title_full | Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages |
| title_fullStr | Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages |
| title_full_unstemmed | Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages |
| title_short | Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages |
| title_sort | placental malaria infection is associated with downregulation of stat 6 and ang 1 in decidual macrophages |
| topic | placental malaria macrophages M1/M2 macrophage polarization transcription factors angiogenic factors |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1497936/full |
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