EVIDENCE FOR A REDUCED CHEMOKINE RESPONSE IN THE LUNGS OF BEIGE MICE INFECTED WITH MYCOBACTERIUM-AVIUM

The basis of the increased susceptibility of beige mice to Mycobacteri um avium infections is still not clearly understood. In this study we examined the growth of three virulent strains of M. avium in beige mic e and normal C57BL/6 controls. Depletion of natural killer (NK) cells by administration of anti-asialo GM1 antisera did not affect the growt h of M. avium in any of the groups of animals. Similarly, interferon-g amma (IFN-gamma) gene-disrupted mice were more susceptible to infectio n than control mice but the growth of M. avium was not further affecte d by NK-cell depletion. In terms of effector immunity, beige mice show ed enhanced expression of IFN-gamma and tumour necrosis factor-alpha. (TNF-alpha) when compared with wild-type C57BL/6 mice. In agreement wi th these results, 1-h and interferon-inducible protein (IP-10) express ion was also higher in beige mice than in wild-type animals, as was ex pression of the chemokines macrophage inflamatory protein-2 (MIP-2) an d macrophage chemotactic protein (MCP-1) during latter stages of the i nfection. However, over the first few weeks of the infection, when the susceptibility of the beige mouse lung first becomes evident, MIP-1 b eta and MIP-2 chemokine expression in the lungs was lower in beige mic e than in wild-type animals. These data indicate, therefore, that the increased susceptibility of beige mice to M. avium infection in the lu ng is not due to lack of NK-cell activity, nor can it be explained in terms of the effector cytokine response. Instead, the lower early expr ession of the neutrophil chemoattractants MIP-1 beta and MIP-2 in the lungs of beige mice tends to suggest that the enhanced susceptibility of these mice to M. avium infection may be due in part to defective re cruitment of neutrophils or other cells responsive to these specific c hemokines.