Fol Marek, Włodarczyk Marcin, Kowalewicz-Kulbat Magdalena, Druszczyńska Magdalena, Krawczyk Krzysztof T, Wawrocki Sebastian, Rudnicka Wiesława, Chmiela Magdalena
Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
Vaccines (Basel). 2022 Apr 14;10(4):615. doi: 10.3390/vaccines10040615.
Mycobacterium tuberculosis infections remain a global health problem in immunosuppressed patients. The effectiveness of BCG (Bacillus Calmette−Guérin), an anti-tuberculosis vaccine, is unsatisfactory. Finding a new vaccine candidate is a priority. We compared numerous immune markers in BCG-susceptible C57BL/6 and BCG-resistant C3H mice who had been injected with 0.9% NaCl (control) or with wild-type BCG or recombinant BCG secreting interleukin (IL)-18 (rBCG/IL-18) and in immunized mice who were immunocompromised with cyclophosphamide (CTX). The inoculation of rBCG/IL-18 in immunocompetent mice increased the percentage of bone marrow myeloblasts and promyelocytes, which were further elevated in the rBCG/IL-18/CTX-treated mice: C57BL/6 mice—3.0% and 11.4% (control) vs. 18.6% and 42.4%, respectively; C3H mice—1.1% and 7.7% (control) vs. 18.4% and 44.9%, respectively, p < 0.05. The bone marrow cells showed an increased mean fluorescence index (MFI) in the CD34 adhesion molecules: C57BL/6 mice—4.0 × 103 (control) vs. 6.2 × 103; C3H mice—4.0 × 103 (control) vs. 8.0 × 103, p < 0.05. Even in the CTX-treated mice, the rBCG/IL-18 mobilized macrophages for phagocytosis, C57BL/6 mice—4% (control) vs. 8%; C3H mice—2% (control) vs. 6%, and in immunocompetent mice, C57BL/6 induced the spleen homing of effector memory CD4+ and CD8+ T cells (TEM), 15% (control) vs. 28% and 8% (control) vs. 22%, respectively, p < 0.05. In conclusion, rBCG/IL-18 effectively induced selected immune determinants that were maintained even in immunocompromised mice.
结核分枝杆菌感染在免疫抑制患者中仍然是一个全球性的健康问题。卡介苗（Bacillus Calmette−Guérin，BCG）作为一种抗结核疫苗，其有效性并不理想。寻找新的候选疫苗是当务之急。我们比较了接种0.9%氯化钠（对照）、野生型卡介苗或分泌白细胞介素（IL）-18的重组卡介苗（rBCG/IL-18）的卡介苗敏感型C57BL/6小鼠和卡介苗耐药型C3H小鼠以及用环磷酰胺（CTX）免疫抑制的免疫小鼠中的多种免疫标志物。在免疫健全的小鼠中接种rBCG/IL-18可增加骨髓成髓细胞和早幼粒细胞的百分比，在接受rBCG/IL-18/CTX治疗的小鼠中这一比例进一步升高：C57BL/6小鼠——对照组分别为3.0%和11.4%，而治疗组分别为18.6%和42.4%；C3H小鼠——对照组分别为1.1%和7.7%，而治疗组分别为18.4%和44.9%，p<0.05。骨髓细胞中CD34黏附分子的平均荧光指数（MFI）增加：C57BL/6小鼠——对照组为4.0×10³，治疗组为6.2×10³；C3H小鼠——对照组为4.0×10³，治疗组为8.0×10³，p<0.05。即使在CTX治疗的小鼠中，rBCG/IL-18也能动员巨噬细胞进行吞噬作用，C57BL/6小鼠——对照组为4%，治疗组为8%；C3H小鼠——对照组为2%，治疗组为6%，而在免疫健全的小鼠中，C57BL/6可诱导效应记忆CD4⁺和CD8⁺T细胞（TEM）归巢至脾脏，对照组分别为15%和28%以及8%和22%，p<0.05。总之，rBCG/IL-18能有效诱导选定的免疫决定因素，即使在免疫受损的小鼠中这些因素也能得以维持。
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