Hematogenous reseeding of the lung in low-dose, aerosol-infected guinea pigs: unique features of the host-pathogen interface in secondary tubercles.

The ability to study the early events in the pathogenesis of pulmonary tuberculosis in guinea pigs following very low dose (3-5 cfu) infection by the respiratory route has revealed that early (10-14 days) extrapulmonary dissemination results in reseeding of previously uninfected lobes of the lung by the hematogenous route. Thus, in every guinea pig, the lung is challenged twice, once by the airway and 2-3 weeks later by the circulatory system. The so called "secondary" pulmonary lesions which result from the bacillemia differ fundamentally from the primary lesions, in part, because the host has already developed a strong T cell mediated immunity when the hematogenous reseeding occurs. Secondary lung lesions in non-vaccinated guinea pigs behave similarly to primary lung lesions in previously vaccinated guinea pigs. Since the secondary, blood-borne lesions are thought to be the "reactivatable foci" which result in reactivation tuberculosis following prolonged persistent infection, it is important to understand the nature of the host-pathogen interaction in secondary lesions. The guinea pig model provides a unique opportunity to examine both the microbial and host factors which constitute that interface.