Toll-like receptor 4 limits transmission of Bordetella bronchiseptica.
Transmission of pathogens has been notoriously difficult to study under laboratory conditions leaving knowledge gaps regarding how bacterial factors and host immune components affect the spread of infections between hosts. We describe the development of a mouse model of transmission of a natural pathogen, Bordetella bronchiseptica, and its use to assess the impact of host immune functions. Although B. bronchiseptica transmits poorly between wild-type mice and mice lacking other immune components, it transmits efficiently between mice deficient in Toll-Like Receptor 4 (TLR4). TLR4-mutant mice were more susceptible to initial colonization, and poorly controlled pathogen growth and shedding. Heavy neutrophil infiltration distinguished TLR4-deficient responses, and neutrophil depletion did not affect respiratory CFU load, but decreased bacterial shedding. The effect of TLR4 response on transmission may explain the extensive variation in TLR4 agonist potency observed among closely related subspecies of Bordetella. This transmission model will enable mechanistic studies of how pathogens spread from one host to another, the defining feature of infectious disease.
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America ; Graduate Program in Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Olivier
O
Rolin
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America ; Graduate Program in Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Will
W
Smallridge
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Michael
M
Henry
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America ; Graduate Program in Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Laura
L
Goodfield
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America ; Graduate Program in Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
David
D
Place
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Eric T
ET
Harvill
D000818:Animals; D057138:Bacterial Shedding; D001885:Bordetella Infections / Q000276:immunology / Q000635:transmission*; D016950:Bordetella bronchiseptica / Q000276:immunology*; D007113:Immunity, Innate; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009296:Nasal Cavity / Q000276:immunology / Q000382:microbiology; D020556:Neutrophil Infiltration; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology / Q000635:transmission*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4