Characterization of the non-specific humoral and cellular antiviral immunity stimulated by the chloroform-methanol residue (CMR) fraction of Coxiella burnetii.
Modulation of the immune response by the chloroform-methanol residue (CMR) of phase I Coxiella burnetii whole cell was studied in Rift Valley fever virus-infected, or in naive endotoxin-non-responder C3H/HeJ mice. A single dose of CMR completely protected the mice from viral infection. Treating virus-infected mice with antibodies directed against interferons alpha/beta (IFN-alpha beta) and gamma (IFN-gamma) eliminated the CMR-induced protection. CMR stimulated the production of high levels of IFN-alpha/beta and 2'-5'-oligoadenylate synthetase activities in sera of the CMR-treated mice. IFN-gamma was present in supernatants of cultured spleen cells of CMR-treated, virus-infected mice, but not in their serum. Priming mice with CMR optimized the release of INF-gamma, interleukin-1 alpha (IL-1 alpha) and IL-6 from splenocytes in vitro. When stimulated in vitro, IL-2 and granulocyte-macrophage stimulating factor (GM-CSF) did not require in vivo priming for release from cultured spleen cells. Fluorescence-assisted cytometry of CMR-treated mouse spleen cells showed there was a CMR-dependent increase in the percentage of T-cells and Ia-positive T-cells. There also was a biphasic increase in the ratio between Th (L3T4) and Ts (Lyt2) cells. Biological activities stimulated by CMR indicate that CMR is a potent immunostimulant, which may modulate specific and non-specific antiviral responses.
Department of Clinical Immunology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
M
M
Zvilich
J C
JC
Williams
D
D
Waag
W R
WR
Rill
R J
RJ
Malli
P
P
Bell
M
M
Kende
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D015415:Biomarkers; D002478:Cells, Cultured; D002725:Chloroform; D016997:Coxiella burnetii / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007111:Immunity, Cellular; D007372:Interferons / Q000096:biosynthesis; D008297:Male; D000432:Methanol; D051379:Mice; D008809:Mice, Inbred C3H; D012295:Rift Valley Fever / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D015415:Biomarkers; D016207:Cytokines; D002725:Chloroform; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D000432:Methanol