Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2

Abstract

Congenitally athymic nude (nu/nu) mice of a BALB/c genetic background were found considerably more resistant to the induction of focal necrotic hepatitis by herpes simplex virus type 2 (HSV-2) than were phenotypically normal littermates (nu/+) or BALB/c mice. The augmented resistance was age dependent, as it was only manifested in mice from 4 to 5 weeks of age. Studies of the course of infection showed that nude mice were able to restrain virus multiplication in the liver far better than normal mice in the early phase of infection. However, they seemed inferior to normal mice in eliminating the infectious process. In vitro investigation of periteonal macrophages revealed that macrophages from 6-weekold nude mice exhibited accelerated spreading and were three times as restrictive in the replication of HSV-2 as macrophages from normal mice. However, no difference was found in the efficiency of adsorption/phagocytosis between macrophages from nude and normal mice. The increased resistance of nude mice could be abolished by blockade of the macrophage function of the mice by silica. Nude mice reconstituted at birth with thymus cells were just as susceptible to infection as normal mice. These data suggest that the increased resistance of nude mice to HSV-2 hepatitis is due to the presence of nonspecifically activated macrophages before infection.

Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide.

“…The normal response of macrophages from nude mice to priming by LPS and MDP may be a phenomenon which contributes to the surprising ability of nude (nu/nu) mice to survive a challenge infection that is lethal to normal (nu/+) littermates (38)(39)(40). Although the reason for the enhanced survival of nude mice remains unclear (40), one hypothesis is that, in the absence of T-cell-mediated immunity, nude mouse macrophages are exposed to increased amounts of bacterial products, and are thereby chronically activated.…”

Antibody‐Dependent Cellular Cytotoxicity and Natural Killer Cytotoxicity of Peritoneal Cells from Nude Mice to Herpes Simplex Virus‐Infected Cells

“…Preliminary characterization using the macrophage inhibitor latex suggests that, as in C57BL/6mice (10), the macrophage is the major peritoneal ADCC effector cell against HSV-infected targets in nude mice ( Table 2). Other studies have similarly revealed enhanced macrophage function of nude mice regard ingviral restriction (17) and tumoricidal activity (15).…”

“…route in limited situations (17,26). These authors have attributed this to high levels of interferon production (26) or increased activity of macrophage-viral restriction (17). Added to this list of enhanced early defense mechanisms against HSV is our finding of increased NKC of cells from nude mice to HSV-infected cells ( Table 1, Figs.…”

“…Several reports have demonstrated a lack of increased susceptibility of nude mice to HSV infection when virus was administered by the i.p. route in limited situations (17,26). These authors have attributed this to high levels of interferon production (26) or increased activity of macrophage-viral restriction (17).…”

Enhanced Phagocytic Activity of Blood Leukocytes in Athymic Nude Mice

“…an enhanced potential for endocytosis and intracellular killing of some bacteria [3] and for suppression of replication of some viruses [21,27]. An analogous activation was found also in spleen and liver macrophages [14,22].…”