title: Early cytokine and antibody responses against Coxiella burnetii in aerosol infection of BALB/c mice.
abstract: Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response-i.e., C. burnetii-specific interferon γ (IFN-γ) production in response to antigen challenge-might be an additional diagnostic. Detection of IFN-γ responses has been used to identify past and chronic Q fever infections, but the IFN-γ response in acute Q fever has not been described. By challenging immunocompetent BALB/c mice with aerosols containing phase I C. burnetii, the timing and extent of IFN-γ recall responses were evaluated in an acute C. burnetii infection. Other cytokines were also measured in an effort to identify other potential diagnostic markers. The data show that after initial expansion of bacteria first in lungs and then in other tissues, the infection was cleared from day 10 onwards as reflected by the decreasing number of bacteria. The antigen-induced IFN-γ production by splenocytes coincided with emergence of IgM phase II antibodies at day 10 postinfection and preceded appearance of IgG antibodies. This was accompanied by the production of proinflammatory cytokines including interleukin (IL) 6, keratinocyte-derived cytokine, and IFN-γ-induced protein 10, followed by monocyte chemotactic protein 1, but not by IL-1β and tumor necrosis factor α, and only very low production of the anti-inflammatory cytokine IL-10. These data suggest that analysis of antigen-specific IFN-γ responses could be a useful tool for diagnosis of acute Q fever. Moreover, the current model of C. burnetii infection could be used to give new insights into immunological factors that predispose to development of persistent infection.
authors.affiliation: Radboud University Medical Center, Department of Internal Medicine, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: Centers for Disease Control and Prevention, Rickettsial Zoonoses Branch, 1600 Clifton Rd, MS G13, Atlanta, GA 30333, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Self
authors.affiliation: Centers for Disease Control and Prevention, Rickettsial Zoonoses Branch, 1600 Clifton Rd, MS G13, Atlanta, GA 30333, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Fitzpatrick
authors.affiliation: Radboud University Medical Center, Department of Internal Medicine, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Radboud University Medical Center, Department of Internal Medicine, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.affiliation: Radboud University Medical Center, Department of Internal Medicine, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Centers for Disease Control and Prevention, Rickettsial Zoonoses Branch, 1600 Clifton Rd, MS G13, Atlanta, GA 30333, USA. Electronic address: gkersh@cdc.gov.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Kersh
mesh_terms: D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D015415:Biomarkers / Q000097:blood*; D016997:Coxiella burnetii / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D011778:Q Fever / Q000276:immunology*; D013997:Time Factors
chemical_list: D000336:Aerosols; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: Cellular immunity; Coxiella burnetii; Cytokines; Interferon-gamma; Q fever; Serology