Does innate immunity favor Brucella dissemination from lungs?

FERRERO, MARIANA; HIELPOS, MS; BALDI, PC

Ouro Preto

Simposio; The Innate Immune Response in the Pathogenesis of Infectious Disease; 2013

Keystone Symposia

Brucellosis is frequently acquired by humans through inhalation of infected aerosols. It produces debilitating flu-like symptoms, and may lead to localized complications such as neurobrucellosis, arthritis, etc. Brucella can survive within several cell types, including macrophages and dendritic cells, leading to chronic infections. We are studying innate immune responses to Brucella mounted by lung cells, and their potential role in either the control or the promotion of Brucella dissemination after airborne infection. We have found that Brucella infects and replicates in human alveolar and bronchial epithelial cells, but induces the secretion of IL-8 and GM-CSF only in bronchial cells. Conditioned medium from infected monocytes induced the secretion of IL-8 and MCP-1 by alveolar and bronchial cells and, conversely, culture supernatants from Brucella-infected bronchial cells induced MCP-1 production by monocytes, suggesting that a local inflammatory response to Brucella may be synergistically mounted by human lung cells. We have also found that Brucella infects and replicates in murine alveolar macrophages (AM) without inducing cytotoxicity. The infection significantly increased the secretion of TNF-α and KC, but elicited very low levels of IL-1β and IL-12. Both infection with Brucella and incubation with heat-killed B. abortus (HKBA) reduced the expression of MHC-II induced by gamma-interferon (IFN-γ) in AM. Experiments using ovalbumin (OVA) and a MHC-II-restricted OVA-specific T cell hybridoma revealed a reduced antigen presentation by AM pretreated with HKBA. These results indicate that Brucella may establish a replicative niche in AM, inducing a modulated inflammatory response and reducing antigen presentation to T cells. Studies are underway to determine whether Brucella-infected AM can migrate through polarized monolayers of lung epithelial cells to serve as Trojan horses for the bacterium.