title: Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.
abstract: In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ(-/-) and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Mohamad Alaa
authors.initials: MA
authors.lastname: Terkawi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Shinuo
authors.initials: S
authors.lastname: Cao
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Herbas
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Paul Franck Adjou
authors.initials: PF
authors.lastname: Moumouni
authors.affiliation: Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Asadullah Hamid
authors.initials: AH
authors.lastname: Pyarokhil
authors.affiliation: Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kondoh
authors.affiliation: Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Igarashi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan gen@obihiro.ac.jp.
authors.forename: Xuenan
authors.initials: X
authors.lastname: Xuan
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D041001:Babesia microti / Q000276:immunology*; D001404:Babesiosis / Q000188:drug therapy / Q000276:immunology*; D004002:Clodronic Acid / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D004002:Clodronic Acid; D007371:Interferon-gamma