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International Immunology, Vol. 11, No. 4, 481-489, April 1999
© 1999 Japanese Society for Immunology

Th1 dominance in the immune response to live Salmonella typhimurium requires bacterial invasiveness but not persistence

Achal Pashine, Beena John, Satyajit Rath, Anna George and Vineeta Bal

National Institute of Immunology, Aruna Asaf Ali Road, New Delhi 110 067, India

Correspondence to: V. Bal

Factors responsible for the predictable generation of Th1 or Th2 immune responses to micro-organisms in vivo are not well characterized, although the ability of antigen presenting cells (APC) to provide co-stimulation, the kinetics of MHC–peptide ligand generation as well as the cytokine environment are all considered important factors for the differential Th1/Th2 priming of T cells. Our earlier findings of an IFN-{gamma}-dominant, Th1-type response to live Salmonella typhimurium (Stm) and a Th2-type response to killed Stm suggested that persistence of viable bacteria might be an important factor in the generation of IFN-{gamma}-dominant responses. Using genetically susceptible and resistant strains of mice to limit bacterial replication and persistence in vivo, we show that mice of the Ityr genotype, capable of a 10-fold better clearance of Stm, mount an IFN-{gamma}-dominant immune response following immunization with live Stm similar to that in the Itys strain. Further, metabolically defective mutants of Stm, aroA and purA, when used in the live form, also elicit IFN-{gamma}-dominant immune responses similar to the wild-type Stm strain despite their inability to proliferate in vivo. While a laboratory strain of Escherichia coli, which is antigenically cross-reactive but non-invasive, elicits hardly any IFN-{gamma} in immune responses, an invasive strain of E. coli induces an IFN-{gamma}-dominant response. These data together indicate that, while entry of bacteria into macrophages is likely to be critical for the generation of IFN-{gamma}-dominant immune responses, their persistence is not.

Keywords: Escherichia coli, IFN-{gamma}, Th2

Transmitting editor: M. Feldman


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