Coinfection with Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis suppresses IL-2 and IFN gamma production and promotes an IL-4 response in C3H/HeJ mice.
Previously we demonstrated that Borrelia burgdorferi transmission by Ixodes scapularis suppressed IL-2 and IFN gamma production and promoted IL-4 production in mice. The present studies were conducted to determine whether coinfection with the human granulocytic ehrlichiosis (HE) agent would promote a Th2 cytokine response in mice. Transmission to the spleen of the agent of human granulocytic ehrlichiosis (aoHGE) and B. burgdorferi occurred 4 and 7 days, respectively, after tick infestation. Coinfection synergized to suppress splenic IL-2 production 7-14 days after tick infestion. Transmission of B. burgdorferi or aoHGE alone significantly decreased splenic IFN gamma 4-7 days after tick infestation, while coinfection suppressed IFN gamma production 7-14 days after tick infestation. Splenic IL-4 production was significantly increased 4 days after coinfection, and by day 10, aoHGE plus B. burgdorferi induced greater splenic IL-4 (57.2 pg/ml, 348% of control values) than either organism transmitted alone (aoHGE, 22.7 pg/ml, B. burgdorferi, 25.1 pg/ml). Coinfection enhanced expansion of splenic T cells, CD4+ lymphocytes and B cells while decreasing CD8+ T cells. These data demonstrate that aoHGE and B. burgdorferi, when cotransmitted, suppress a systemic IL-2 and IFN gamma response, while strongly promoting systemic IL-4 production in the susceptible host. The antigen(s) responsible for this polarization are unknown and will be the subject of future studies.
Zeidner
N S
NS
Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, PO Box 2087, Rampart Road, Foothills Campus, Fort Collins, CO 80522, USA. naz2@cdc.gov
Dolan
M C
MC
Massung
R
R
Piesman
J
J
Fish
D
D
D000818:Animals; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D004536:Ehrlichia / Q000235:genetics / Q000276:immunology*; D016873:Ehrlichiosis / Q000150:complications / Q000276:immunology* / Q000635:transmission; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018884:Ixodes / Q000382:microbiology; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000635:transmission; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma