Basophils amplify type 2 immune responses, but do not serve a protective role, during chronic infection of mice with the filarial nematode Litomosoides sigmodontis.
Chronic helminth infections induce a type 2 immune response characterized by eosinophilia, high levels of IgE, and increased T cell production of type 2 cytokines. Because basophils have been shown to be substantial contributors of IL-4 in helminth infections, and because basophils are capable of inducing Th2 differentiation of CD4(+) T cells and IgE isotype switching in B cells, we hypothesized that basophils function to amplify type 2 immune responses in chronic helminth infection. To test this, we evaluated basophil function using the Litomosoides sigmodontis filaria model of chronic helminth infection in BALB/c mice. Time-course studies showed that eosinophilia, parasite Ag-specific CD4(+) T cell production of IL-4 and IL-5 and basophil activation and IL-4 production in response to parasite Ag all peak late (6-8 wk) in the course of L. sigmodontis infection, after parasite-specific IgE has become detectable. Mixed-gender and single-sex worm implantation experiments demonstrated that the relatively late peak of these responses was not dependent on the appearance of circulating microfilariae, but may be due to initial low levels of parasite Ag load and/or habitation of the developing worms in the pleural space. Depletion of basophils throughout the course of L. sigmodontis infection caused significant decreases in total and parasite-specific IgE, eosinophilia, and parasite Ag-driven CD4(+) T cell proliferation and IL-4 production, but did not alter total worm numbers. These results demonstrate that basophils amplify type 2 immune responses, but do not serve a protective role, in chronic infection of mice with the filarial nematode L. sigmodontis.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. mtorrero@usuhs.mil
Marina N
MN
Torrero
Marc P
MP
Hübner
David
D
Larson
Hajime
H
Karasuyama
Edward
E
Mitre
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D049109:Cell Proliferation; D002908:Chronic Disease; D004802:Eosinophilia / Q000276:immunology / Q000469:parasitology; D005260:Female; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
D000947:Antigens, Helminth; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E