Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model
Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for en...
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MDPI AG
2021-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/3/245 |
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| author | Jeng-Chang Chen Liang-Shiou Ou Ming-Ling Kuo Li-Yun Tseng Hsueh-Ling Chang Shiang-Chi Chen Cheng-Hsun Chiu |
| author_facet | Jeng-Chang Chen Liang-Shiou Ou Ming-Ling Kuo Li-Yun Tseng Hsueh-Ling Chang Shiang-Chi Chen Cheng-Hsun Chiu |
| author_sort | Jeng-Chang Chen |
| collection | DOAJ |
| description | Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed <i>Salmonella</i> Typhimurium. Recipients with in utero exposure to <i>Salmonella</i> antigens or adoptive transfer of microbial antigen-loaded fetal macrophages were examined for immune responses to <i>Salmonella</i> antigens and resistance to virulent <i>Salmonella</i> challenge. Fetal exposure to microbial antigens or adoptive transfer of microbial antigen-loaded fetal macrophages could confer antigen-specific adaptive immunity. However, protective immunity against lethal <i>Salmonella</i> challenge was only granted to those receiving heat-killed <i>Salmonella</i> antigens, presenting as heightened recall responses of serum anti-lipopolysaccharide immunoglobulins and interferon-gamma. In immunized recipients surviving <i>Salmonella</i> challenge, their serum transfer to succeeding recipients provided immediate protection from lethal <i>Salmonella</i> challenge in preference to lymphocyte transfer, indicating a more active role of humoral immunity in the prevention of <i>Salmonella</i> invasiveness. Our study sheds insight on the role of fetal macrophages in immunogenicity to transplacental pathogens regardless of fetal lymphocyte maturity, paving the way for fetal macrophage therapies to enhance vaccine responsiveness or increase resistance to pathogenic microorganisms in perinatal life. |
| first_indexed | 2024-03-09T06:06:45Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T06:06:45Z |
| publishDate | 2021-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-df20d29caff4415388ffde517e1264e72023-12-03T12:03:10ZengMDPI AGBiomedicines2227-90592021-03-019324510.3390/biomedicines9030245Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine ModelJeng-Chang Chen0Liang-Shiou Ou1Ming-Ling Kuo2Li-Yun Tseng3Hsueh-Ling Chang4Shiang-Chi Chen5Cheng-Hsun Chiu6Department of Surgery, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDivision of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDivision of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanPediatric Research Center, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanPediatric Research Center, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDepartment of Nursing, Taipei Medical University, Taipei 110, TaiwanDivision of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDespite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed <i>Salmonella</i> Typhimurium. Recipients with in utero exposure to <i>Salmonella</i> antigens or adoptive transfer of microbial antigen-loaded fetal macrophages were examined for immune responses to <i>Salmonella</i> antigens and resistance to virulent <i>Salmonella</i> challenge. Fetal exposure to microbial antigens or adoptive transfer of microbial antigen-loaded fetal macrophages could confer antigen-specific adaptive immunity. However, protective immunity against lethal <i>Salmonella</i> challenge was only granted to those receiving heat-killed <i>Salmonella</i> antigens, presenting as heightened recall responses of serum anti-lipopolysaccharide immunoglobulins and interferon-gamma. In immunized recipients surviving <i>Salmonella</i> challenge, their serum transfer to succeeding recipients provided immediate protection from lethal <i>Salmonella</i> challenge in preference to lymphocyte transfer, indicating a more active role of humoral immunity in the prevention of <i>Salmonella</i> invasiveness. Our study sheds insight on the role of fetal macrophages in immunogenicity to transplacental pathogens regardless of fetal lymphocyte maturity, paving the way for fetal macrophage therapies to enhance vaccine responsiveness or increase resistance to pathogenic microorganisms in perinatal life.https://www.mdpi.com/2227-9059/9/3/245macrophagefetal immunization<i>Salmonella</i>maternal infectionvertical transmission |
| spellingShingle | Jeng-Chang Chen Liang-Shiou Ou Ming-Ling Kuo Li-Yun Tseng Hsueh-Ling Chang Shiang-Chi Chen Cheng-Hsun Chiu Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model Biomedicines macrophage fetal immunization <i>Salmonella</i> maternal infection vertical transmission |
| title | Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model |
| title_full | Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model |
| title_fullStr | Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model |
| title_full_unstemmed | Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model |
| title_short | Fetal Macrophages Exposed to <i>Salmonella</i> Antigens Elicit Protective Immunity Against Overwhelming <i>Salmonella</i> Challenge in A Murine Model |
| title_sort | fetal macrophages exposed to i salmonella i antigens elicit protective immunity against overwhelming i salmonella i challenge in a murine model |
| topic | macrophage fetal immunization <i>Salmonella</i> maternal infection vertical transmission |
| url | https://www.mdpi.com/2227-9059/9/3/245 |
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