Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
PLoS One. 2021 Oct 13;16(10):e0258491. doi: 10.1371/journal.pone.0258491. eCollection 2021.
Mastitis is an inflammation of the mammary gland in the breast and is typically due to bacterial infection. In malaria-endemic areas, mastitis with accompanying fever can be challenging to differentiate from malaria. At the same time, it is unclear whether malaria infection is directly involved in the development of mastitis. In the present study, whether mastitis develops during infection with malaria parasites was investigated using a rodent malaria model with Plasmodium berghei (P. berghei; Pb) ANKA. The course of parasitemia in postpartum mice infected with Pb ANKA was similar to the course in infected virgin mice. However, infected postpartum mice died earlier than did infected virgin mice. In addition, the weight of pups from mice infected with Pb ANKA was significantly reduced compared with pups from uninfected mice. The macroscopic and histological analyses showed apparent changes, such as destruction of the alveolus wall and extensive presence of leukocytes, in mammary gland tissue in mice infected during the postpartum period. The findings suggest that women during the postpartum period are more vulnerable to complications when infected with malaria parasites, particularly women who do not acquire protective immunity against malaria parasites. Based on the proteomic analysis, IFN-γ signaling pathway-related proteins in mammary gland tissue of the infected postpartum mice were increased. Our results indicate that inflammation induced by IFN-γ, a proinflammatory cytokine, may contribute to negative histological changes in mammary gland tissue of postpartum mice infected with Pb ANKA. In IFN-γ receptor 1-deficient (IFNGR1-KO) mice, the histological changes in mammary gland tissue of the infected postpartum wild-type mice were improved to almost normal mammary gland structure. Furthermore, weight loss in pups delivered by infected IFNGR1-KO postpartum mice was not observed. Taken together, these findings indicate that inflammation induced by IFN-γ is associated with development of mastitis in postpartum mice infected with Pb ANKA. The present study results may increase our understanding of how disease aggravation occurs during postpartum malaria.
乳腺炎是乳房的乳腺炎症，通常是由细菌感染引起的。在疟疾流行地区，伴有发热的乳腺炎可能难以与疟疾区分开来。同时，尚不清楚疟疾感染是否直接参与乳腺炎的发生。在本研究中，使用 Plasmodium berghei（P. berghei；Pb）ANKA 啮齿动物疟疾模型来研究乳腺炎是否在感染疟原虫期间发生。产后感染 Pb ANKA 的小鼠的寄生虫血症过程与感染未感染的 virgin 小鼠的寄生虫血症过程相似。但是，感染后的哺乳期小鼠比感染后的 virgin 小鼠更早死亡。此外，与未感染的小鼠相比，来自感染 Pb ANKA 的小鼠的幼仔的体重明显减轻。宏观和组织学分析表明，在产后感染的小鼠的乳腺组织中出现了明显的变化，例如肺泡壁的破坏和白细胞的广泛存在。这些发现表明，处于产后阶段的女性在感染疟原虫时更容易发生并发症，尤其是那些未获得针对疟原虫的保护性免疫的女性。基于蛋白质组学分析，感染产后小鼠的乳腺组织中 IFN-γ 信号通路相关蛋白增加。我们的结果表明，IFN-γ（一种促炎细胞因子）诱导的炎症可能导致感染 Pb ANKA 的产后小鼠的乳腺组织发生负性组织学变化。在 IFN-γ 受体 1 缺陷（IFNGR1-KO）小鼠中，感染产后野生型小鼠的乳腺组织的组织学变化得到改善，几乎恢复为正常乳腺结构。此外，未观察到由感染 IFNGR1-KO 的产后小鼠所生幼仔的体重减轻。总之，这些发现表明，IFN-γ 诱导的炎症与感染 Pb ANKA 的产后小鼠乳腺炎的发生有关。本研究结果可能增加我们对产后疟疾期间疾病恶化发生机制的理解。
