Innate resistance to Listeria monocytogenes in tumor-bearing mice.
We have previously described the isolation, cloning, and characterization of a tumorigenic murine fibrosarcoma, designated JBS. Growth of JBS tumors in syngeneic mice initiates an anti-tumor immune response that initially manifests as progressive splenic hyperplasia and an increased proliferative ability in cultured splenocytes. In animals with tumors progressing beyond the 2 cm stage there is a reduction in spleen size and a gradual decrease in splenocyte proliferative abilities, leading to anergy at heavy tumor burdens (>3.5 cm). During the phase of immune hyperresponsiveness in tumor-bearing mice clearance of Listeria monocytogenes by components of the innate immune system is increased. This heightened resistance to infection is most likely macrophage-mediated because these mice demonstrate an increased ability to recruit macrophages to the peritoneal cavity during Listeria infection. In addition, these macrophages are highly activated in vivo as evidenced by an elevated capacity to express class II MHC (Ia) molecules. This increase in macrophage activation status is coincident with an increased capacity of splenocytes from tumor-bearing mice to secrete IFN-gamma. In mice with much heavier tumor burdens (>3.5 cm), down-regulation of the immune response leads to a reduction in peritoneal macrophage numbers, decreased macrophage Ia expression, and diminished splenic clearance of L. monocytogenes. Our data demonstrate that activation of macrophages distal to the tumor site occurs as an initial consequence of tumor growth. It is only in mice with very heavy tumor burdens that functionality of macrophages is sufficiently suppressed to allow increased splenic growth of L. monocytogenes.
Gahan
C G
CG
Department of Microbiology, University College, Cork, Ireland.
Barrett
J R
JR
O'Brien
M G
MG
O'Sullivan
G C
GC
Shanahan
F
F
Collins
J K
JK
D000818:Animals; D005354:Fibrosarcoma / Q000150:complications / Q000276:immunology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D008088:Listeriosis / Q000150:complications / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000150:complications / Q000276:immunology*
D007371:Interferon-gamma