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Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microtiInfection in Mice

Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microtiInfection in Mice

Authors :
Terkawi, Mohamad Alaa
Cao, Shinuo
Herbas, Maria S.
Nishimura, Maki
Li, Yan
Moumouni, Paul Franck Adjou
Pyarokhil, Asadullah Hamid
Kondoh, Daisuke
Kitamura, Nobuo
Nishikawa, Yoshifumi
Kato, Kentaro
Yokoyama, Naoaki
Zhou, Jinlin
Suzuki, Hiroshi
Igarashi, Ikuo
Xuan, Xuenan
Source :
Infection and Immunity; October 2014, Vol. 83 Issue: 1 p8-16, 9p
Publication Year :
2014

Abstract

ABSTRACTIn 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. microtiinfection 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. microtiinfection 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. microtiand imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.

Details

Language :
English
ISSN :
00199567 and 10985522
Volume :
83
Issue :
1
Database :
Supplemental Index
Journal :
Infection and Immunity
Publication Type :
Periodical
Accession number :
ejs34431502
Full Text :
https://doi.org/10.1128/IAI.02128-14