Wild-type (WT) C57BL/6 mice infected intraperitoneally with Trypanosoma congolense survive for more than 30 days. C57BL/6 mice deficient in inducible nitric oxide synthase (iNOS？/？) and infected with 103 or parasites do not control the parasitemia and survive for only or days, respectively. Bloodstream trypanosomes of iNOS？/？ mice infected with ？？T. congolense had a significantly higher ratio of organisms in the S+G2+M phases of the cell cycle than trypanosomes in WT mice. We have reported that IgM anti-VSG-mediated phagocytosis of T. congolense by macrophages inhibits nitric oxide (NO) synthesis via CR3 (CD11b/CD18). Here, we show that during the first parasitemia, but not at later stages of infection, T. congolense-infected CD11b？/？ mice produce more NO and have a significantly lower parasitemia than infected WT mice. We conclude that induced NO contributes to the control of parasitemia by inhibiting the growth of the trypanosomes. 1. Introduction Trypanosoma congolense is a protozoan pathogen of cattle and other livestock. The parasite causes N’gana in livestock, one form of the disease complex collectively known as African trypanosomiases [1]. In the mammalian host, the whole parasite is covered with a glycoprotein coat of a single molecular species, called variant surface glycoprotein (VSG) [2]. In host defense against infection, macrophages play an important role through their ability to remove specific substances from the blood stream via various receptors, such as complement receptors, Fc-receptors, scavenger receptors, and mannose receptors [3, 4]. The control of parasitemia in African trypanosomiasis is mediated by at least two known mechanisms: (1) antibody-mediated phagocytosis [5–9] and (2) to a lesser degree, by antibody/complement-mediated lysis [10–13]. A third mechanism, that is, release of trypanotoxic NO by macrophages has been demonstrated in vitro for T. brucei and T. congolense [14–18]. The role of NO in vivo has been controversial. We had speculated that NO might be involved in the control of T. congolense infections [9]. There is evidence that NO does not contribute to control of T. brucei in vivo [19, 20] but does contribute to control of T. congolense infections [21, 22]. We found that IgG2a anti-VSG antibody-mediated phagocytosis of T. congolense enhances the synthesis of NO by macrophages, whereas IgM anti-VSG antibody-mediated phagocytosis inhibited synthesis of NO [7, 14]. The inhibition of NO synthesis apparently increased with increasing amounts of IgM anti-VSG [14]. We further observed that macrophages of CD11b？/？ mice
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