Virus-like particle-induced protection against MRSA pneumonia is dependent on IL-13 and enhancement of phagocyte function.
The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13-dependent mechanisms.
Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59717-3610, USA. agnieszka.rynda@montana.edu
Agnieszka
A
Rynda-Apple
Erin
E
Dobrinen
Mark
M
McAlpine
Amanda
A
Read
Ann
A
Harmsen
Laura E
LE
Richert
Matthew
M
Calverley
Kyler
K
Pallister
Jovanka
J
Voyich
James A
JA
Wiley
Ben
B
Johnson
Mark
M
Young
Trevor
T
Douglas
Allen G
AG
Harmsen
D056704:Adaptive Immunity; D000281:Administration, Intranasal; D000818:Animals; D058491:Bacterial Load; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
D039521:CD11c Antigen; D018793:Interleukin-13; D013209:Staphylococcal Vaccines; D058425:Vaccines, Virus-Like Particle