See Jia-Xiang, Samudi Chandramathi, Saeidi Alireza, Menon Nivedita, Choh Leang-Chung, Vadivelu Jamuna, Shankar Esaki M
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
Tropical Infectious Disease Research and Education Center (TIDREC), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
PLoS Negl Trop Dis. 2016 Mar 14;10(3):e0004503. doi: 10.1371/journal.pntd.0004503. eCollection 2016 Mar.
Burkholderia pseudomallei (B. pseudomallei), the causative agent of melioidosis, is a deadly pathogen endemic across parts of tropical South East Asia and Northern Australia. B. pseudomallei can remain latent within the intracellular compartment of the host cell over prolonged periods of time, and cause persistent disease leading to treatment difficulties. Understanding the immunological mechanisms behind persistent infection can result in improved treatment strategies in clinical melioidosis.
Ten-day LD50 was determined for the small-colony variant (SCV) and its parental wild-type (WT) via intranasal route in experimental BALB/c mice. Persistent B. pseudomallei infection was generated by administrating sub-lethal dose of the two strains based on previously determined LD50. After two months, peripheral blood mononuclear cells (PBMCs) and plasma were obtained to investigate host immune responses against persistent B. pseudomallei infection. Lungs, livers, and spleens were harvested and bacterial loads in these organs were determined.
Based on the ten-day LD50, the SCV was ~20-fold less virulent than the WT. The SCV caused higher bacterial loads in spleens compared to its WT counterparts with persistent B. pseudomallei infection. We found that the CD4+ T-cell frequencies were decreased, and the expressions of PD-1, but not CTLA-4 were significantly increased on the CD4+ and CD8+ T cells of these mice. Notably, persistent infection with the SCV led to significantly higher levels of PD-1 than the WT B. pseudomallei. Plasma IFN-γ, IL-6, and IL-17A levels were elevated only in SCV-infected mice. In addition, skewed plasma Th1 and Th17 responses were observed in SCV-infected mice relative to WT-infected and uninfected mice.
B. pseudomallei appears to upregulate the expression of PD-1 on T cells to evade host immune responses, which likely facilitates bacterial persistence in the host. SCVs cause distinct pathology and immune responses in the host as compared to WT B. pseudomallei.
类鼻疽杆菌（Burkholderia pseudomallei）是类鼻疽病的病原体，是一种致命的病原体，在热带东南亚部分地区和澳大利亚北部流行。类鼻疽杆菌可在宿主细胞的细胞内区室中长期潜伏，并导致持续性疾病，从而导致治疗困难。了解持续性感染背后的免疫机制有助于改善类鼻疽病的临床治疗策略。
通过鼻内途径在实验性BALB/c小鼠中测定小菌落变体（SCV）及其亲本野生型（WT）的十日半数致死剂量（LD50）。根据先前确定的LD50，通过给予两种菌株的亚致死剂量来产生持续性类鼻疽杆菌感染。两个月后，获取外周血单核细胞（PBMC）和血浆，以研究宿主针对持续性类鼻疽杆菌感染的免疫反应。采集肺、肝和脾，并测定这些器官中的细菌载量。
根据十日LD50，SCV的毒力比WT低约20倍。在持续性类鼻疽杆菌感染的情况下，与WT相比，SCV在脾脏中导致更高的细菌载量。我们发现，这些小鼠的CD4+T细胞频率降低，并且CD4+和CD8+T细胞上PD-1的表达显著增加，但CTLA-4的表达没有增加。值得注意的是，与WT类鼻疽杆菌相比，SCV的持续性感染导致PD-1水平显著更高。仅在感染SCV的小鼠中，血浆干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）和白细胞介素-17A（IL-17A）水平升高。此外，相对于感染WT和未感染的小鼠，在感染SCV的小鼠中观察到血浆Th1和Th17反应偏向。
类鼻疽杆菌似乎上调T细胞上PD-1的表达以逃避宿主免疫反应，这可能有助于细菌在宿主体内持续存在。与WT类鼻疽杆菌相比，SCV在宿主体内引起不同的病理和免疫反应。
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