Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria
Malaria and babesiosis, the two primary intraerythrocytic protozoan diseases of humans, have been reported in multiple cases of co-infection in endemic regions. As the geographic range and incidence of arthropod-borne infectious diseases is being affected by climate change, co-infection cases with P...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00193/full |
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| author | Artemis Efstratiou Eloiza May S. Galon Guanbo Wang Kousuke Umeda Daisuke Kondoh Mohamad Alaa Terkawi Mohamad Alaa Terkawi Aiko Kume Mingming Liu Aaron Edmond Ringo Huanping Guo Yang Gao Seung-Hun Lee Jixu Li Paul Franck Adjou Moumouni Yoshifumi Nishikawa Hiroshi Suzuki Ikuo Igarashi Xuenan Xuan |
| author_facet | Artemis Efstratiou Eloiza May S. Galon Guanbo Wang Kousuke Umeda Daisuke Kondoh Mohamad Alaa Terkawi Mohamad Alaa Terkawi Aiko Kume Mingming Liu Aaron Edmond Ringo Huanping Guo Yang Gao Seung-Hun Lee Jixu Li Paul Franck Adjou Moumouni Yoshifumi Nishikawa Hiroshi Suzuki Ikuo Igarashi Xuenan Xuan |
| author_sort | Artemis Efstratiou |
| collection | DOAJ |
| description | Malaria and babesiosis, the two primary intraerythrocytic protozoan diseases of humans, have been reported in multiple cases of co-infection in endemic regions. As the geographic range and incidence of arthropod-borne infectious diseases is being affected by climate change, co-infection cases with Plasmodium and Babesia are likely to increase. The two parasites have been used in experimental settings, where prior infection with Babesia microti has been shown to protect against fatal malarial infections in mice and primates. However, the immunological mechanisms behind such phenomena of cross-protection remain unknown. Here, we investigated the effect of a primary B. microti infection on the outcome of a lethal P. chabaudi challenge infection using a murine model. Simultaneous infection with both pathogens led to high mortality rates in immunocompetent BALB/c mice, similar to control mice infected with P. chabaudi alone. On the other hand, mice with various stages of B. microti primary infection were thoroughly immune to a subsequent P. chabaudi challenge. Protected mice exhibited decreased levels of serum antibodies and pro-inflammatory cytokines during early stages of challenge infection. Mice repeatedly immunized with dead B. microti quickly succumbed to P. chabaudi infection, despite induction of high antibody responses. Notably, cross-protection was observed in mice lacking functional B and T lymphocytes. When the role of other innate immune effector cells was examined, NK cell-depleted mice with chronic B. microti infection were also found to be protected against P. chabaudi. Conversely, in vivo macrophage depletion rendered the mice vulnerable to P. chabaudi. The above results show that the mechanism of cross-protection conferred by B. microti against P. chabaudi is innate immunity-based, and suggest that it relies predominantly upon the function of macrophages. Further research is needed for elucidating the malaria-suppressing effects of babesiosis, with a vision toward development of novel tools to control malaria. |
| first_indexed | 2024-12-21T20:31:31Z |
| format | Article |
| id | doaj.art-6a03d58795f0417e9ef8c613e3f9bd34 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T20:31:31Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-6a03d58795f0417e9ef8c613e3f9bd342022-12-21T18:51:12ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-04-011010.3389/fcimb.2020.00193515440Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine MalariaArtemis Efstratiou0Eloiza May S. Galon1Guanbo Wang2Kousuke Umeda3Daisuke Kondoh4Mohamad Alaa Terkawi5Mohamad Alaa Terkawi6Aiko Kume7Mingming Liu8Aaron Edmond Ringo9Huanping Guo10Yang Gao11Seung-Hun Lee12Jixu Li13Paul Franck Adjou Moumouni14Yoshifumi Nishikawa15Hiroshi Suzuki16Ikuo Igarashi17Xuenan Xuan18National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanDepartment of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanDepartment of Orthopedic Surgery, Hokkaido University, Sapporo, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanMalaria and babesiosis, the two primary intraerythrocytic protozoan diseases of humans, have been reported in multiple cases of co-infection in endemic regions. As the geographic range and incidence of arthropod-borne infectious diseases is being affected by climate change, co-infection cases with Plasmodium and Babesia are likely to increase. The two parasites have been used in experimental settings, where prior infection with Babesia microti has been shown to protect against fatal malarial infections in mice and primates. However, the immunological mechanisms behind such phenomena of cross-protection remain unknown. Here, we investigated the effect of a primary B. microti infection on the outcome of a lethal P. chabaudi challenge infection using a murine model. Simultaneous infection with both pathogens led to high mortality rates in immunocompetent BALB/c mice, similar to control mice infected with P. chabaudi alone. On the other hand, mice with various stages of B. microti primary infection were thoroughly immune to a subsequent P. chabaudi challenge. Protected mice exhibited decreased levels of serum antibodies and pro-inflammatory cytokines during early stages of challenge infection. Mice repeatedly immunized with dead B. microti quickly succumbed to P. chabaudi infection, despite induction of high antibody responses. Notably, cross-protection was observed in mice lacking functional B and T lymphocytes. When the role of other innate immune effector cells was examined, NK cell-depleted mice with chronic B. microti infection were also found to be protected against P. chabaudi. Conversely, in vivo macrophage depletion rendered the mice vulnerable to P. chabaudi. The above results show that the mechanism of cross-protection conferred by B. microti against P. chabaudi is innate immunity-based, and suggest that it relies predominantly upon the function of macrophages. Further research is needed for elucidating the malaria-suppressing effects of babesiosis, with a vision toward development of novel tools to control malaria.https://www.frontiersin.org/article/10.3389/fcimb.2020.00193/fullPlasmodium chabaudimalariaBabesia microtibabesiosisinfectionmacrophages |
| spellingShingle | Artemis Efstratiou Eloiza May S. Galon Guanbo Wang Kousuke Umeda Daisuke Kondoh Mohamad Alaa Terkawi Mohamad Alaa Terkawi Aiko Kume Mingming Liu Aaron Edmond Ringo Huanping Guo Yang Gao Seung-Hun Lee Jixu Li Paul Franck Adjou Moumouni Yoshifumi Nishikawa Hiroshi Suzuki Ikuo Igarashi Xuenan Xuan Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria Frontiers in Cellular and Infection Microbiology Plasmodium chabaudi malaria Babesia microti babesiosis infection macrophages |
| title | Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria |
| title_full | Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria |
| title_fullStr | Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria |
| title_full_unstemmed | Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria |
| title_short | Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria |
| title_sort | babesia microti confers macrophage based cross protective immunity against murine malaria |
| topic | Plasmodium chabaudi malaria Babesia microti babesiosis infection macrophages |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00193/full |
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