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Differential Requirements for Soluble and Transmembrane Tumor Necrosis Factor in the Immunological Control of Primary and Secondary Listeria monocytogenes Infection

Author:
Musicki, Korana, Briscoe, Helen, Tran, Stephen, Britton, Warwick J., Saunders, Bernadette M.
Source:
Infection and immunity 2006 v.74 no.6 pp. 3180-3189
ISSN:
0019-9567
Subject:
Listeria monocytogenes, T-lymphocytes, chemokines, immunity, inflammation, liver, macrophages, mice, mortality, nitric oxide synthase, tumor necrosis factors
Abstract:
The relative contributions of transmembrane tumor necrosis factor (memTNF)and soluble tumor necrosis factor (solTNF) in innate and adaptiveimmunity are poorly defined. We examined the capacities of wild-type(WT) mice, TNF⁻/⁻ mice, and memTNF mice,which express only transmembrane TNF, to control primary and secondaryListeria monocytogenes infections. Soluble TNF was notrequired for induction or maintenance of protective immunity against alow-dose (200-CFU) Listeria infection. In contrast toTNF⁻/⁻ mice, both WT and memTNF mice clearedthe bacilli within 10 days and were fully protected against rechallengewith a lethal infective dose. Furthermore, T cells transferred fromimmune mice, but not from naïve, WT, and memTNF mice, protectedTNF⁻/⁻ recipients against an otherwiselethal infection. By contrast, infection with a higher dose ofListeria (2,000 CFU) clearly demonstrated that solTNF isrequired to coordinate an optimal protective inflammatory response.memTNF mice were more susceptible to a high-dose infection, and theyexhibited delayed bacterial clearance, increased inflammation, andnecrosis in the liver that resulted in 55% mortality. The dysregulatedinflammation was accompanied by prolonged elevated expression of mRNAsfor several chemokines as well as the macrophage effector moleculesinducible nitric oxide synthase and LRG-47 in the livers of memTNF micebut not in the livers of WT mice. These data demonstrated that memTNFis sufficient for establishing protective immunity against a primarylow-dose Listeria infection but that solTNF is required foroptimal control of cellular inflammation and resistance to a primaryhigh-dose infection. By contrast, memTNF alone is sufficient forresolution of a secondary, high-dose infection and for the transfer ofprotective immunity with memory Tcells.
Agid:
267911