American Society for Investigative Pathology, February 2013, Vol 5, No. 1

Hot off the Press

Virus-Like Particle-Induced Protection Against MRSA Pneumonia Is Dependent on IL-13 and Enhancement of Phagocyte Function.
Agnieszka Rynda-Apple,* Erin Dobrinen,* Mark McAlpine,* Amanda Read,* Ann Harmsen,* Laura E. Richert,* Matthew Calverley,* Kyler Pallister,* Jovanka Voyich,* James A. Wiley,* Ben Johnson,† Mark Young,‡ Trevor Douglas,† and Allen G. Harmsen*

From the Departments of Immunology and Infectious Diseases,* Chemistry and Biochemistry,† and Plant Sciences and Plant Pathology,‡ Montana State University, Bozeman, Montana

Am J Pathol 2012, 181:196-210; DOI: 10.1016/j.ajpath.2012.03.018.

By using the small heat shock protein (sHsp) nanoparticles that closely resemble virus-like particles (VLPs) we are able to induce a state of immune readiness in the lung in preparation of a future insult. This state of immune preparedness is characterized by an enhanced and accelerated migration of innate immune cells (like neutrophils and monocytes) to the lung that resembles the immune response to an actual pathogen. However, in contrast to the pathogen-initiated recruitment, VLP-mediated recruitment occurs in the absence of the host-immune response-induced tissue damage. Nasal immunization of mice with these VLPs prior to, or immediately after lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hrs of challenge. The mechanism of this VLP-mediated protection relies on innate immunity, as complete recovery is seen in VLP-dosed immunodeficient SCID mice, but not in wild type mice depleted of Ly6G+ (neutrophils) or CD11c+ cells (dendritic cells and alveolar macrophages). Early production of IL-13 by CD11c+ cells induced by VLP immunization is essential for this protection. Our findings indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing, and reducing inflammation-induced tissue damage via IL-13-dependent mechanisms.