The role of TLR4 in Brucella infection remains controversial. Some studies suggest that TLR4 is required to control Brucella replication in the mouse (Campos et al., 2004; Copin et al., 2007; Macedo et al., 2008) ; others indicate that TLR4 is not involved (Weiss et al., 2005; Barquero-Calvo et al., 2007) . The use of different Brucella strains/species in these experiments may account for the observed differences. The influence of the route of infection on the role of TLRs in studies with other pathogens suggests a need to do so with brucellosis, as is the role of TLR-mediated innate immunity in the development of adaptive immune response. These studies employed intraperitoneal (i.p.) inoculation, which is not a typical route for Brucella infection. As a result of these reports, the consensus of scientific opinion is that MyD88 contributes significantly to the control of Brucella infection while TLR-based signaling plays a lesser role at best. The absence of any role for TLR signaling is consistent with results indicating that the Brucella protein TcpB interrupts TLR-based signaling by promoting degradation of MyD88 adaptor like protein, MAL (Chaudhary et al., 2012) , and modification of Brucella LPS reduces agonist activity (Duenas et al., 2004) . However, these studies have been restricted to an atypical route of exposure, and the potential for differential TLR expression associated with different tissues has not been considered (Juarez et al., 2010) . Since inhalation represents a major concern to public health, experiments were undertaken to determine the role of TLR signaling in the control of Brucella infection following aerosol exposure. The current study, investigates the roles of TLR2, TLR4, and MyD88 in clearance of Brucella following respiratory exposure and development of adaptive immune response against Brucella. Since the mucosal/respiratory system is the primary portal of entry for human infection documented in many laboratory incidents and relevant to biothreats, it is important to understand the pathogenesis and immune responses resulting from aerosol exposure.