登革熱病毒是一種在血液中生存致病原，患者感染後會導致登革熱。在登革熱病毒初次感染中，病毒通常會導致輕微的登革熱。然而，再次感染不同的登革熱時，登革熱病毒可誘發危及生命的登革出血熱（DHF）或登革休克綜合徵（DSS），主要是通過引起血小板減少和血管通透性增加而導致血漿滲漏和出血。我們之前的研究表明，糖尿病（DM）患者由於異常免疫信號傳遞而造成免疫缺陷，並且其對自然免疫細胞在對某些感染的反應非常微弱。根據之前臨床的數據顯示，與無DM的患者相比，DM患者感染登革熱後病毒的數量更高，發展成登革熱重症的機會更高。因此，我們建立登革熱病毒感染糖尿病小鼠動物模型研究初次感染的免疫反應。在動物模型部分，我們將每隻小鼠的2×106PFU登革熱病毒作為對照組，經由靜脈注射感染STAT1-/-- 小鼠。我們使用血管通透性分析和組織病理分析登革病毒感染小鼠的肺，肝和小腸組織中的發炎和出血的情況。我們通過血管通透性測定發現了登革熱病毒感染的STAT1-/- 小鼠的肝臟和小腸中血管通透性增強。我們還觀察到組織病理分析登革病毒感染STAT1-/- 小鼠的小腸出血和免疫細胞浸潤。接著我們將每隻小鼠經由靜脈主射感染2x106PFU的登革熱病毒至鏈脲佐菌素（STZ）誘導的糖尿病小鼠。我們發現在每隻小鼠感染2×106PFU登革熱病毒的糖尿病小鼠的小腸中增強的血管通透性。我們觀察了登革病毒感染的糖尿病小鼠模型中自然類淋巴細胞（ILCs）的變化。我們發現在糖尿病小鼠感染的登革熱病毒的小腸中ILC1和ILC3增加。這些結果顯示糖尿病人的免疫缺陷，和先前報告可導致發展成登革重症的免疫缺損有相似類似的地方。

Dengue virus is a blood-borne pathogen that causes dengue fever in patients. In the primary dengue virus infection, the virus usually causes mild dengue fever. In the secondary infection, however, the virus can induce life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which lead to plasma leakage and hemorrhage by causing thrombocytopenia and increased vascular permeability. Our previous studies showed that patients with diabetes mellitus (DM) are immunodeficient due to aberrant immune signal transduction and their innate immune cells were severely weakened in the responses to certain infections. The data from the previous epidemic also showed that dengue patients with DM had higher viral loads and a higher chance of severe disease in comparison with patients without DM. Therefore, we investigated the immune responses to primary dengue viral infection in a diabetic mouse model. We found enhanced vascular permeability in the liver and small intestine of the STAT1-/- mouse with dengue virus infection. We also observed hemorrhage and leukocyte infiltration in the small intestine of STAT1-/- mice with dengue virus infection. We then intravenously infected the streptozotocin (STZ)-induced diabetic mouse. We found enhanced vascular permeability in the small intestine of the diabetic mouse infected with dengue virus. We also investigated the changes in innate lymphoid cells (ILCs) in the primary dengue virus-infected diabetic mice model. We found increased ILC1 and ILC3 in the small intestine of the diabetic mouse infected with dengue virus. The abnormal immune responses in subjects with DM hence may be similar to the immunodeficient conditions reported to predispose to more severe dengue virus infection.

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