Babesia bovis Immunity: In Vitro and in Vivo Evidence for IL‐10 Regulation of IFN‐γ and iNOS^a

Abstract

IL-10 has been shown to have profound immunoregulatory attributes and in the bovine appears to downregulate both Th1- and Th2-like responses. Using RT-PCR, we demonstrate IL-10 in vitro down-regulation of mRNA expression of iNOS, the cytokines involved in nitric oxide signal transduction initiation (IFN-gamma and TNF-alpha), and other mononuclear phagocyte associate cytokines. In addition, using RT-PCR with peripheral blood leukocytes and spleen leukocytes, the Griess reaction, and a killing assay, we provide evidence for the importance of iNOS in a successful immune response to B. bovis infection and for high and persistent IL-10 mRNA expression when the immune response is unsuccessful. We also provide evidence that antibody developed early after an initial infection appears to lack protective attributes (neutralizing and opsonic). Together, the data suggests that IL-10 and IFN-gamma are critical molecules involved in the response to this intraerythrocytic protozoan infection.

Tick Passage Results in Enhanced Attenuation of Babesia bovis

“…This suggests that a threshold parasitemia level is required to cause severe clinical disease, consistent with previous work by Goff et al using the T2Bo_vir strain (17). Interestingly, in two separate experiments, animals infected with the same virulent or attenuated T2Bo strain after tick passage had divergent clinical presentations, with retention of the virulence phenotype in T2Bo_vir-infected animals and a surprising lack of virulence in T2Bo_att-infected animals.…”

Cytokine and Inducible Nitric Oxide Synthase Gene Expressions in Peripheral Blood Mononuclear Cells and Related Clinical Characteristics in Theileria orientalis sergenti-Infected Calves

“…The expression of iNOS mRNA in PBMC and plasma nitrite/ nitrate concentration was expected to increase at least in the high susceptibilities as per in vitro findings, but it was not so. Similar phenomena have been reported in Trypanosoma-infected cattle [9,26], mice [8], and Toxoplasma gondii-infected mice [25] and a decrease in plasma L-arginine concentration was recorded. The depleted L-arginine levels were thought to be as a result of arginase activity of host cells and consumption of L-arginine by the parasite, and was considered to be a determinant factor for the modulation of NO production [8].…”

“…One is a calcium-dependent system involving a constitutive NOS while the other, which is likely to be more relevant for pathogenesis, involves an iNOS that is activated by cytokines. NO reacts with oxygen to produce nitrite and/or nitrate, which are termed as reactive nitrogen intermediates and are toxic to intraerythrocytic protozoa [9,22]. In our study, a decrease in plasma nitrite/nitrate with progress in infection was observed in all susceptibility calves.…”

“…Furthermore, no trace of the expression of iNOS mRNA was found in these calves. On in vitro examination, the addition of IFN-γ to mouse peritoneal macrophages [5] and bovine peripheral macrophages [9], induced nitrite secretion, and further addition of TNF-α increased nitrite secretion significantly. The expression of iNOS mRNA in PBMC and plasma nitrite/ nitrate concentration was expected to increase at least in the high susceptibilities as per in vitro findings, but it was not so.…”

Immunization with Recombinant Surface Antigens p26 with Freund's Adjuvants against Babesia rodhaini Infection.

“…Therefore, our results indicate that the antibody response did not correlate the protection against the challenge infection, and cell-mediated immunity rather than humoral immunity is involved in the mechanism behind the Failure of IFN-γ-deficient mice to induce protective immunity against challenge infection provided further evidence that cell-mediated immunity is very important for the protection induced with the recombinant antigens. The importance of IFN-γ in the protective immunity has been suggested in Babesia [5,8,14] as well as other intracellular protozoan infections such as Plasmodium, Toxoplasma, and Trypanosoma [1,11,15,25]. Further studies on IFN-γ as well as other cytokine responses such as TNF-α, IL-10 and IL-12, and studies on other antigens and adjuvants enhancing specific immune responses will deepen the understanding of the immune mechanism and stimulate the development of vaccines against the Babesia infection.…”