Essential role for humoral immunity during Ehrlichia infection in immunocompetent mice.
Although cellular immunity is essential for host defense during intracellular bacterial infections, humoral immunity can also play a significant role in host defense during infection by some intracellular bacteria, including the ehrlichiae. Antibodies can protect susceptible SCID mice from fatal Ehrlichia chaffeensis infection, an observation that has been hypothesized to involve the opsonization of bacteria released from host cells. To determine whether humoral immunity plays an essential role during ehrlichia infection in immunocompetent mice, we utilized a murine model of fatal monocytotropic ehrlichiosis caused by Ixodes ovatus ehrlichia. Mice lacking either B cells or FcgammaRI were unable to resolve a low-dose (sublethal) I. ovatus ehrlichia infection, which suggested that humoral immunity is essential for resistance. Polyclonal sera generated in I. ovatus ehrlichia-infected mice recognized a conserved ehrlichia outer membrane protein and, when administered to infected mice, caused a significant decrease in bacterial infection. Mice experimentally depleted of complement, or deficient for complement receptors 1 and 2, were also susceptible to sublethal I. ovatus ehrlichia infection, as were mice that lacked the phox91 subunit of NADPH oxidase. The data are consistent with a mechanism whereby bacteria released from infected cells are lysed directly by complement or undergo antibody-mediated FcgammaR-dependent phagocytosis and subsequent exposure to reactive oxygen intermediates. The findings suggest mechanisms whereby antibodies contribute to immunity against intracellular bacteria in immunocompetent mice.
Yager
Eric
E
The Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York 12201-0509, USA.
Bitsaktsis
Constantine
C
Nandi
Bisweswar
B
McBride
Jere W
JW
Winslow
Gary
G
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D018469:Ehrlichia chaffeensis; D016873:Ehrlichiosis / Q000276:immunology* / Q000378:metabolism; D007106:Immune Sera / Q000276:immunology; D007121:Immunocompetence; D018884:Ixodes / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011951:Receptors, Complement / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; C485701:Fcgr1 protein, mouse; D007106:Immune Sera; D017382:Reactive Oxygen Species; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D003165:Complement System Proteins; D019255:NADPH Oxidases