Tumor necrosis factor induces resistance of macrophages to Legionella pneumophila infection.
Legionella pneumophila is an ubiquitous opportunistic intracellular pathogen that replicates readily in thioglycollate-elicited peritoneal macrophages from genetically susceptible A/J mice. Treatment of macrophage cultures in vitro with tumor necrosis factor-alpha (TNF-alpha) induced resistance of the macrophages to infection by Legionella as compared with control macrophages treated with medium alone. Addition of small amounts of monoclonal antibody to TNF-alpha restored susceptibility of the macrophages. Furthermore, antibody to the proinflammatory cytokine interleukin-1 (IL-1) alpha/beta increased resistance, but recombinant IL-1 had little effect. Such decreased susceptibility to Legionella growth in anti-IL-1 antibody-treated cultures corresponded with enhanced levels of TNF-alpha in the supernatants of the treated cells. An antibody to another proinflammatory cytokine with known immunoregulatory properties (i.e., IL-6) had little or no effect on the ability of the macrophages to be infected by Legionella and, furthermore, treatment with recombinant IL-6, similar to recombinant IL-1, did not modify the ability of the cells to be infected in vitro. These results indicate that TNF-alpha is important in controlling L. pneumophila replication, and IL-1 can regulate TNF-alpha levels, affecting susceptibility of macrophages to infection with an intracellular opportunistic pathogen like Legionella.
McHugh
S L
SL
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
Newton
C A
CA
Yamamoto
Y
Y
Klein
T W
TW
Friedman
H
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D020022:Genetic Predisposition to Disease; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016952:Legionella pneumophila / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008805:Mice, Inbred A; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000906:Antibodies; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha