Induction of IL-10-producing CD1dhighCD5+ regulatory B cells following Babesia microti-infection.
BACKGROUND
Understanding the induction of immune regulatory cells upon helminth infection is important for understanding the control of autoimmunity and allergic inflammation in helminth infection. Babesia microti, an intraerythrocytic protozoan of the genus Babesia, is a major cause of the emerging human disease babesiosis, an asymptomatic malaria-like disease. We examined the influence of acute B. microti infection on the development of regulatory B cells together with regulatory T cells.


RESULTS
Our data demonstrate that B cells stimulated in vitro with B. microti produce interleukin (IL)-10. This cytokine is also secreted by B cells isolated from B. microti-infected mice in response to lipopolysaccharide stimulation. In addition, high levels of IL-10 were detected in the serum of mice after infection with B. microti. The frequency of IL-10-producing CD1d(high)CD5(+) regulatory B cells (Bregs) and CD4(+)CD25(+)FoxP3(+) T cells increased during the course of B. microti infection. Furthermore, adoptive transfer of IL-10-producing B cells induced by B. microti infection led to increased susceptibility of recipient mice to infection with B. microti. In contrast, experiments with B cell-deficient (µMT) mice demonstrated that lack of B cells enhances susceptibility to B. microti infection.


CONCLUSIONS
This study is the first demonstration of the expansion of Bregs following infection by an intraerythrocytic protozoan parasite. These data suggest that B. microti infection in mice provides an excellent model for studying Breg-mediated immune responses and begins to elucidate the mechanism by which helminth infection regulates autoimmunity and allergic inflammation.
Division of Malaria & Parasitic Disease, Korea National Institute of Health, Cheongwon-gun, Chungbuk, Korea.
Young-Il
YI
Jeong
Sung-Hee
SH
Hong
Shin-Hyeong
SH
Cho
Won-Ja
WJ
Lee
Sang-Eun
SE
Lee
D019264:Adoptive Transfer; D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D041001:Babesia microti / Q000502:physiology*; D001404:Babesiosis / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018956:CD5 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006790:Host-Parasite Interactions; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009929:Organ Size; D018512:Parasitemia / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D013154:Spleen / Q000276:immunology / Q000469:parasitology / Q000473:pathology
D055610:Antigens, CD1d; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma