Resistance to infection: looking for new genes

Genetic factors in resistance to infection, somewhat neglected with the development of microbiology, are again receiving careful attention. Although there are numerous reports of infection resulting from deficiencies in, for example, immunoglobulins or complement components, specific abnormalities in resistance associated with particular HLA groups have been unexpectedly rare. In mice, the Ity gene on chromosome 1, which is important in resistance to Salmonella typhimurium infection, may well be identical with the Lsh and Bcg genes concerned with resistance to Leishmania donovani and Mycobacterium bovis BCG. The most likely common factor determining resistance to three such disparate organisms is the macrophage, but direct evidence of its role is lacking. The high and low antibody-producing strains of mice selected by BIOZZI [2] are respectively sensitive and resistant to many intracellular infections including S. thyphimurium. Experiments with hybrids between Biozzi mice and other inbred strains suggest that the high line carries the Itys (salmonella susceptibility gene) plus another gene increasing susceptibility. Low line mice carry the Ityr gene plus another gene increasing resistance. Inbred mice are invaluable for analogizing gene interactions which, once understood, can be looked for in man.