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The Journal of Immunology, 2002, 169: 4450-4459.
Copyright © 2002 by The American Association of Immunologists

The Innate Immune Response Differs in Primary and Secondary Salmonella Infection1

Alun C. Kirby, Ulf Yrlid and Mary Jo Wick2

Department of Cell and Molecular Biology, Section for Immunology, Lund University, Lund, Sweden

This study examines innate immunity to oral Salmonella during primary infection and after secondary challenge of immune mice. Splenic NK and NKT cells plummeted early after primary infection, while neutrophils and macrophages (M{phi}) increased 10- and 3-fold, respectively. In contrast, immune animals had only a modest reduction in NK cells, no loss of NKT cells, and a slight increase in phagocytes following secondary challenge. During primary infection, the dominant sources of IFN-{gamma} were, unexpectedly, neutrophils and M{phi}, the former having intracellular stores of IFN-{gamma} that were released during infection. IFN-{gamma}-producing phagocytes greatly outnumbered IFN-{gamma}-producing NK cells, NKT cells, and T cells during the primary response. TNF-{alpha} production was also dominated by neutrophils and M{phi}, which vastly outnumbered NKT cells producing this cytokine. Neither T cells nor NK cells produced TNF-{alpha} early during primary infection. The TNF-{alpha} response was reduced in a secondary response, but remained dominated by neutrophils and M{phi}. Moreover, no significant IFN-{gamma} production by M{phi} was associated with the secondary response. Indeed, only NK1.1+ cells and T cells produced IFN-{gamma} in these mice. These studies provide a coherent view of innate immunity to oral Salmonella infection, reveal novel sources of IFN-{gamma}, and demonstrate that immune status influences the nature of the innate response.




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