Complement component C1q plays a critical role in VLRA/VLRC-mediated immune response
| Autor: | Jingjing Lu, Yue Pang, Yue Shan, Qinghua Ma, Xiaoping Song, Meng Gou, Jun Li, Feng Sun, Yinglun Han, Qingwei Li, Peng Su, Xin Liu, Huaixiu Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cytotoxicity
Immunologic Fish Proteins 0301 basic medicine Immunology Embryonic Development Microbiology 03 medical and health sciences 0302 clinical medicine Immune system Variable lymphocyte receptor Antigen Gene expression Animals Lymphocytes Cells Cultured biology Complement C1q Lamprey Immunity Wild type Lampreys Complement Pathway Mannose-Binding Lectin Complement C3 biology.organism_classification Aeromonas hydrophila Up-Regulation Receptors Antigen 030104 developmental biology Gene Knockdown Techniques Larva Lectin pathway Gram-Negative Bacterial Infections 030215 immunology Developmental Biology |
| Zdroj: | Developmental & Comparative Immunology. 111:103750 |
| ISSN: | 0145-305X |
| DOI: | 10.1016/j.dci.2020.103750 |
| Popis: | In jawless vertebrates, the lamprey complement component C1q (LC1q) acts as a lectin and activates lamprey complement component C3 (LC3) in association with mannose-binding lectin (MBL)-associated serine protease (MASP) via the lectin pathway. Furthermore, LC1q may interact with variable lymphocyte receptor B (VLRB) in a complex with antigens and mediate the activation of LC3, leading to cytolysis. In the present study, we found, for the first time, that LC1q plays a critical role in VLRA/VLRC-mediated immune response. Escherichia coli, Shigella flexneri, Aeromonas hydrophila, Pseudomonas plecoglossicida, Aeromonas allosaccharophila, P. luteola, Brevundimonas diminuta, and Bacillus cereus were isolated from infected Lampetra morii in our laboratory and identified using the 16s rRNA method. A. hydrophila was confirmed as a rapidly spreading lethal pathogen in the larvae of L. morii and was used in subsequent immune stimulation experiments. The results of real-time quantitative polymerase chain reaction (Q-PCR) and immunofluorescence analyses indicated that the RNA and protein expression levels of LC1q were upregulated following exposure to 107 cfu/mL of A. hydrophila, compared to the levels of the naive group. We obtained LC1q morphants (LC1q MO) of lamprey larvae by morpholino-mediated knockdowns. We found that LC1q played key roles in the embryonic development of lamprey. The median lethal time (LT50) of LC1q MO larvae was 2 d after being exposed to the pathogens, whereas the LT50 of control MO was 5 d. The drastic decrease in LT50 values after LC1q knockdown implies that LC1q plays a critical role in lamprey immune response. Gene expression profiles of LC1q-deficient A. hydrophila, control MO A. hydrophila, wild type A. hydrophila, and naive 1-month-old ammocoetes larvae were compared by examining the expression levels of a selected panel of orthologous genes. It is worth mentioning that LC1q MO affected the VLRA+/VLRC + population genes but did not affect the VLRB + populations. Immunohistochemical data indicated that LC1q deficiency also affected VLRA and VLRC but not VLRB. Thus, LC1q plays a critical role in VLRA/VLRC-mediated immune response in lamprey. |
| Databáze: | OpenAIRE |
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