Modulation of Intracellular Growth ofListeria monocytogenesin Human Enterocyte Caco‐2 Cells by Interferon‐γ and Interleukin‐6: Role of Nitric Oxide and Cooperation with Antibiotics

Abstract

The influence of interferon (IFN)-γ and interleukin (IL)-6 on the intracellular growth of Listeria monocytogenes phagocytosed from the apical pole was examined in polarized Caco-2 cells. IFN-γ (from the apical pole) and IL-6 (from the basolateral pole) considerably reduced the bacterial intracellular growth, an effect largely abolished by 1-monomethyl arginine. Both cytokines caused overexpression of inducible nitric oxide synthase. IL-6, but not IFN-γ, caused a partial restriction of L. monocytogenes in phagosomes and largely prevented the cytosolic forms from being surrounded by actin. Ampicillin was bacteriostatic in unstimulated cells but modestly bactericidal in cells treated with IFN-γ and IL-6. Azithromycin (a macrolide) was fairly bactericidal and sparfloxacin (a fluoroquinolone) highly bactericidal in all situations. IFN-γ and IL-6 may therefore be important determinants in the protection of epithelial cells from intracellular multiplication of L. monocytogenes. Ampicillin may fail in their absence, requiring the use of other antibiotics such as the fluoroquinolones.