Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice.
Previous studies have suggested that both inflammatory monocytes and neutrophils are important for controlling acute toxoplasmosis in the mouse model. To test the role of these cell types, we used monoclonal antibody (MAb) RB6-8C5 to deplete both subsets of cells or MAb 1A8 to selectively remove neutrophils. RB6-8C5 MAb-treated mice succumbed to oral infection with Toxoplasma gondii, similar to Ccr2(-/-) mice, which are deficient in monocyte recruitment but have normal neutrophils. In contrast, mice treated with MAb 1A8 controlled parasite replication and survived acute infection. Ccr2(-/-) mice suffered from acute ileitis and inflammation in the spleen that was associated with a lack of inflammatory monocytes and elevated numbers of neutrophils. RB6-8C5 MAb-treated C57BL/6 mice also suffered from intestinal pathology and splenic damage, although this was less extensive due to the reduced numbers of neutrophils. Neutrophil-depleted infected wild-type mice displayed no pathological changes, compared to untreated infected controls. Collectively, these observations demonstrate the critical role of inflammatory monocytes during the acute infection with the parasite T. gondii and reveal that neutrophils are not protective but rather contribute to the pathology.
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Ildiko R
IR
Dunay
Anja
A
Fuchs
L David
LD
Sibley
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007079:Ileitis / Q000469:parasitology / Q000473:pathology; D047589:Leukocyte Reduction Procedures; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D054390:Receptors, CCR2 / Q000172:deficiency; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
D000911:Antibodies, Monoclonal; C515335:Ccr2 protein, mouse; D016207:Cytokines; D054390:Receptors, CCR2