The complex mechanism of antibody-mediated clearance of Bordetella from the lungs requires TLR4.
Although the antibacterial effects of Abs are well studied in in vitro systems, the in vivo effects of Abs cannot always be accurately predicted. Complicated cross-talk between different effector functions of Abs and various arms of the immune system can affect their activities in vivo. Using the mouse respiratory pathogen Bordetella bronchiseptica, we examined the mechanisms of Ab-mediated clearance of bacteria from the respiratory tract. Interestingly, although TLR4 was not necessary for protective immunity following infection, it was required for rapid bacterial clearance in mice that were vaccinated or adoptively transferred Abs. TLR4 was important for the rapid recruitment of neutrophils that are necessary for Ab-mediated bacterial clearance via a mechanism that requires both FcgammaR and CR3. These data are consistent with a model in which TLR4-mediated inflammatory responses aid in the recruitment of neutrophils, which phagocytose Ab- and complement-opsonized bacteria via FcgammaRs and CR3. Although pattern recognition receptors are known to be involved in innate immunity and the generation of adaptive immunity, their contributions to specific adaptive immune functions should be considered in ongoing efforts to improve vaccine-induced protective immunity.
Kirimanjeswara
Girish S
GS
Immunology Research Laboratories, Department of Biomedical Veterinary Sciences, Pennsylvania State University, University Park 16802, USA.
Mann
Paul B
PB
Pilione
Mylisa
M
Kennett
Mary J
MJ
Harvill
Eric T
ET
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001885:Bordetella Infections / Q000276:immunology*; D016950:Bordetella bronchiseptica / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D017452:Receptors, IgG / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D000907:Antibodies, Bacterial; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014612:Vaccines