Concurrent infections with Trypanosoma brucei and Nippostrongylus brasiliensis in mice deficient in inducible nitric oxide.
Concurrent infection with Trypanosoma brucei (Tb) delays the normal protective responses of mice to the gastrointestinal parasite Nippostrongylus brasiliensis (Nb). The course of such infections was followed in mice genetically deficient in inducible nitric oxide synthase (INOS) to assess the role of nitric oxide (NO) in this effect. The time course of trypanosome infection in INOS deficient (INOS-/-) mice was similar to that in wild type (WT) and heterozygote (INOS+/-) mice but did not result in NO production. Although concurrent infection with Tb increased initial susceptibility to Nb in INOS-/- mice, the immune-mediated loss of N. brasiliensis and the associated decline in faecal egg output occurred more rapidly then in WT and INOS+/- littermates. Concurrent infection with trypanosomes markedly suppressed Concanavalin A (ConA)-induced in vitro proliferation of splenic lymphocytes in all groups, but had little effect on the responses of mesenteric node lymphocytes. Trypanosome infection was also associated with increased early release of interferon-gamma and reduced IL-5 from lymphocytes stimulated in vitro with ConA, but did not affect later release of IL-5. The overall similarity of proliferative and cytokine responses in WT, INOS+/- and INOS-/- mice suggest that the suppressive effects of T. brucei on N. brasiliensis infection do not simply reflect depressed lymphocyte responsiveness or altered cytokine profiles. NO appears to be involved in suppression only of the later phases of the host responses to Nb.
Chiejina
Samuel
S
School of Life and Environmental Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Goyal
Prem
P
Li
Chris
C
Wakelin
Derek
D
D000818:Animals; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000302:isolation & purification; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010270:Parasite Egg Count; D051381:Rats; D017208:Rats, Wistar; D017206:Strongylida Infections / Q000150:complications / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000150:complications / Q000276:immunology*
D015848:Interleukin-5; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat