Early pregnancy affects expression of Toll-like receptor signaling members in ovine spleen

Abstract Toll-like receptors (TLRs) are involved to the maternal immune tolerance. The spleen is essential for adaptive immune reactions. However, it is unclear that early pregnancy regulates TLR-mediated signalings in the maternal spleen. The purpose of this study was to investigate the effects of early pregnancy on expression of TLR signaling members in the ovine spleen. Ovine spleens were collected at day 16 of the estrous cycle, and at days 13, 16 and 25 of pregnancy (n = 6 for each group). Real-time quantitative PCR, western blot and immunohistochemistry analysis were used to detect TLR signaling members, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR9, myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6) and interleukin-1-receptor-associated kinase 1 (IRAK1). The results showed that expression levels of TLR2, TLR4 and IRAK1 were downregulated, but expression levels of TLR3, TLR5, TLR7, TLR9, TRAF6 and MyD88 were increased during early pregnancy. In addition, MyD88 protein was located in the capsule, trabeculae and splenic cords of the maternal spleen. This paper reports for the first time that early pregnancy has effects on TLR signaling pathways in the ovine spleen, which is beneficial for understanding the maternal immune tolerance during early pregnancy.

Early pregnancy affects expression of Toll-like receptor signaling members in ovine spleen

Toll-like receptors (TLRs) are involved to the maternal immune tolerance. The spleen is essential for adaptive immune reactions. However, it is unclear that early pregnancy regulates TLR-mediated signalings in the maternal spleen. The purpose of this study was to investigate the effects of early pregnancy on expression of TLR signaling members in the ovine spleen. Ovine spleens were collected at day 16 of the estrous cycle, and at days 13, 16 and 25 of pregnancy (n = 6 for each group). Real-time quantitative PCR, western blot and immunohistochemistry analysis were used to detect TLR signaling members, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR9, myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6) and interleukin-1-receptor-associated kinase 1 (IRAK1). The results showed that expression levels of TLR2, TLR4 and IRAK1 were downregulated, but expression levels of TLR3, TLR5, TLR7, TLR9, TRAF6 and MyD88 were increased during early pregnancy. In addition, MyD88 protein was located in the capsule, trabeculae and splenic cords of the maternal spleen. This paper reports for the first time that early pregnancy has effects on TLR signaling pathways in the ovine spleen, which is beneficial for understanding the maternal immune tolerance during early pregnancy.(AU)

Acute and chronic histopathologic changes in wild typeTLR-2-/-, TLR-4-/-, TLR-6-/-, TLR-9-/-, CD14-/-, and MyD-88-/- mice experimentally infected with Plasmodium chabaudi

Malaria is caused by protozoan parasites of the genus Plasmodium, which is transmitted by Anopheline mosquitoes. Experimental murine models using rodent malaria are useful for studying pathologic aspects of severe malaria. We evaluated histopathologic lesions of TLR-2-/-, TLR-4-/-, TLR-6-/-, TLR-9-/-, CD14-/- and MyD88-/- mice experimentally infected with Plasmodium chabaudi. Frequencies and severity of microscopic lesions in the spleen and liver at one and four weeks post infection (wpi) were determined. At one wpi, adherence of macrophages to the endothelial surface was the most evident change, whereas at four wpi there was marked accumulation of cytoplasmic pigment in macrophages in the liver and spleen. Lesions were not markedly influenced by the absence of TLRs, MyD88 or CD14. Our findings suggest that acute and chronic phases of murine infection with P. chabaudi are characterized by distinct lesions. In addition, TLRs and MyD88 are not essential to promote these lesions during P. chabaudi infection.(AU)

Acute and chronic histopathologic changes in wild type or TLR-2-/-, TLR-4-/-, TLR-6-/-, TLR-9-/-, CD14-/-, and MyD-88-/- mice experimentally infected with Plasmodium chabaudi

Malaria is caused by protozoan parasites of the genus Plasmodium, which is transmitted by Anopheline mosquitoes. Experimental murine models using rodent malaria are useful for studying pathologic aspects of severe malaria. We evaluated histopathologic lesions of TLR-2-/-, TLR-4-/-, TLR-6-/-, TLR-9-/-, CD14-/-, and MyD-88-/- mice experimentally infected with Plasmodium chabaudi. Frequencies and severity of microscopic lesions in the spleen and liver at one and four weeks post infection (wpi) were determined. At one wpi, adherence of macrophages to the endothelial surface was the most evident change, whereas at four wpi there was marked accumulation of cytoplasmic pigment in macrophages in the liver and spleen. Lesions were not markedly influenced by the absence of TLRs, MyD88 or CD14. Our findings suggest that acute and chronic phases of murine infection with P. chabaudi are characterized by distinct lesions. In addition, TLRs and MyD88 are not essential to promote these lesions during P. chabaudi infection.