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Autoregulation by interferons provides an endogenous 'priming' signal for LPS-responsive macrophages

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

S.N. Vogel

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

RT-PCR technology was used to evaluate endogenous levels of IFN-, β, and mRNA in macrophages derived from LPS-responsive (C3H/OuJ) and LPS-hyporesponsive (C3H/HeJ) mice. IFN mRNA levels were found to be consistently higher in the LPS-responsive macrophages. That these IFNs may be part of an autocrine loop is supported by the observations that treatment of macrophages, in vitro, with IFN- or IFN-β induces IFN- mRNA and, conversely, that exogenous IFN- treatment results in increased detection of both IFN-a and IFN-β mRNA species. In vitro 'priming' of LPS-hyporesponsive macrophages with either IFN- or IFN- causes these cells to be activated by a polyI:C triggering signal, in a manner equivalent to that seen for LPS-'primed' C3H/OuJ macrophages. Thus, low levels of endogenous IFNs, which induce each other bidirectionally, may provide a replenishable source of 'primed' macrophages, that are more plentiful in Lpsⁿ mice and that are capable of being 'triggered' to functional maturity during an immune response.

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