Immune responses induced in cattle by virulent and attenuated Mycobacterium bovis strains: Correlation of delayed-type hypersensitivity with ability of strains to grow in macrophages

Comparison of immune responses induced in cattle by virulent and attenuated strains of Mycobacterium bovis will assist in identifying responses associ ated with resistance or susceptibility to disease. Four strains of Al. bovi s, one which is virulent in guinea pigs (WAg201) and three which are attenu ated in guinea pigs tan isoniazid-resistant strain [WAg405], ATCC 35721, an d BCG) were compared for their abilities to induce immune responses in catt le and to grow in bovine lung alveolar macrophage cultures. Extensive macro scopic lesions were found only in cattle inoculated with the virulent ill, bovis strain. Strong antibody responses to ill. bovis culture filtrate, as well as persistently high levels of gamma interferon and interleukin-2 rele ased from purified protein derivative (PPD)-stimulated peripheral blood lym phocyte cultures, were observed in the cattle inoculated with the virulent strain compared to those inoculated with the attenuated strains. All cattle inoculated with the virulent strain or two of the attenuated strains (WAg4 05 and ATCC 35721) elicited strong delayed-type hypersensitivity responses to PPD in skin tests, while animals inoculated with BCG induced only a weak response. The three strains which produced strong skin test responses prol iferated well in bovine alveolar macrophages and induced high levels of pro inflammatory cytokine mRNAs compared to BCG, Our study showed that skin tes t responsiveness to PPD correlated with the ability of the strains to grow in alveolar macrophages rather than to their pathogenicity in cattle.