The momentous discovery of phagocytic activity in teleost B cells has caused a dramatic paradigm shift from the belief that phagocytosis is performed mainly by professional phagocytes derived from ...common myeloid progenitor cells, such as macrophages/monocytes, neutrophils, and dendritic cells. Recent advances on phagocytic B cells and their microbicidal ability in teleost fish position B cells at the crossroads, bridging innate with adaptive immunity. Most importantly, an increasing body of experimental evidence demonstrates that, in both teleosts and mammals, phagocytic B cells can recognize, take up, and destroy particulate antigens and then present those processed antigens to CD4
T cells to elicit adaptive immune responses and that the phagocytosis is mediated by pattern recognition receptors and involves multiple cytokines. Thus, current findings collectively indicate that teleost phagocytic B cells, as well as their counterpart mammalian B1-B cells, can be considered one kind of professional phagocyte. The aim of this review is to summarize recent advances regarding teleost phagocytic B cells, with a particular focus on the recognizing receptors and modulating mechanisms of phagocytic B cells and the process of antigen presentation for T-cell activation. We also attempt to provide new insights into the adaptive evolution of the teleost fish phagocytic B cell on the basis of its innate and adaptive roles.
This study intends to investigate nivolumab's efficacy and adverse effects in combination with lenvatinib in treating advanced hepatocellular carcinoma (HCC). For this purpose, ninety-two patients ...with unresectable advanced HCC admitted were enrolled and were divided into the control group (N=46) and the observation group (N=46) according to the random number table. The control group was treated with lenvatinib while the observation group was treated with nivolumab combined with lenvatinib. The efficacy, adverse effects, liver function, completion rate, interruption and discontinuation of treatment, drug reduction, serum tumor markers, and immune function were compared between the two groups. Also, changes in the expression of some genes that regulate the cell cycle (P53, RB1, Cyclin-D1, c-fos, and N-ras) were investigated in the development of this cancer. According to the results, ORR and DCR (45.65%, 78.26%) in the observation group were higher than those (23.91%, 54.35%) in the control group (P<0.05); The incidence of adverse reactions in the observation group was slightly higher than that of the control group, but the difference was not significant (P>0.05); The rate of completion, interruption, discontinuation of treatment and drug reduction did not differ significantly between two groups (P>0.05); After treatment, the serum ALT, AST, TBIL, and GGT levels decreased and were lower in observation group than in control group (P<0.05); The serum tumor markers AFP, ENO1, GPC3, CEA levels decreased in both groups after treatment, and were lower in the observation group than in control group (P<0.05); CD3, CD4, CD8, and NK levels were improved in the observation group and worsened in the control group, and CD3, CD4, and NK levels were higher in the observation group and lower in the control group after treatment (P<0.05). All in all, nivolumab combined with lenvatinib for advanced hepatocellular carcinoma can improve tumor control, reduce tumor load, and improve liver function and immune function. Common adverse reactions include fatigue, loss of appetite, elevated blood pressure, hand-foot skin reaction, diarrhea, and rash, which should be controlled during treatment.
Collectin-K1 (CL-K1) is a multifunctional C-type lectin that has been identified as playing a crucial role in innate immunity. It can bind to carbohydrates on pathogens, leading to direct ...neutralization, agglutination, and/or opsonization, thereby inhibiting pathogenic infection. In this study, we investigated a homolog of CL-K1 (
CL-K1) in Nile tilapia (
) and its role in promoting the clearance of the pathogen
(
) and enhancing the antibacterial ability of the fish. Our analysis of bacterial load displayed that
substantially reduced the amount of
in tissues of the liver, spleen, anterior kidney, and brain in Nile tilapia. Furthermore, examination of tissue sections revealed that
CL-K1 effectively alleviated tissue damage and inflammatory response in the liver, anterior kidney, spleen, and brain tissue of tilapia following
infection. Additionally,
1 was found to decrease the expression of the pro-inflammatory factor
and migration inhibitor
, while increasing the expression of anti-inflammatory factor
and chemokine
in the spleen, anterior kidney, and brain tissues of tilapia. Moreover, statistical analysis of survival rates demonstrated that
CL-K1 significantly improved the survival rate of tilapia after infection, with a survival rate of 90%. Collectively, our findings suggest that
CL-K1 plays a vital role in the innate immune defense of resisting bacterial infection in Nile tilapia. It promotes the removal of bacterial pathogens from the host, inhibits pathogen proliferation in vivo, reduces damage to host tissues caused by pathogens, and improves the survival rate of the host.
The complement system is composed of a complex protein network and is pivotal to innate immunity. Complement 3 (C3) is a critical protein in the complement cascade and participates in complement ...activation and immune defense. In this study, C3 from Nile tilapia (
) was cloned and its function in resisting pathogen infection was characterized. The full length of OnC3 open reading frame is 4974 bp, encoding 1657 aa, and the predicted protein mass weight is 185.93 kDa. The OnC3 amino acid sequence contains macroglobulin domains. The expression pattern of OnC3 mRNA in the tissues of healthy fish was detected, with the highest in the liver and the lowest in the muscle. After challenged with
and
, the expression of OnC3 mRNA was significantly up-regulated in the liver, spleen, and head kidney. Further, the recombinant OnC3 protein alleviated the inflammatory response and pathological damage of tissues after infected with
. Moreover, the OnC3 promoted the phagocytosis of monocytes/macrophages to
. The data obtained in this study provide a theoretical reference for in-depth understanding of C3 in host defense against bacterial infection and the immunomodulatory roles in teleost fish.
Tartrate-resistant acid phosphatase type 5 (TRAP5) is an enzyme that is highly expressed in activated macrophages and osteoclasts and plays important biological functions in mammalian immune defense ...systems. In the study, we investigated the functions of tartrate-resistant acid phosphatase type 5b from
(OnTRAP5b). The OnTRAP5b gene has an open reading frame of 975 bp, which encodes a mature peptide consisting of 302 amino acids with a molecular weight of 33.448 kDa. The OnTRAP5b protein contains a metallophosphatase domain with metal binding and active sites. Phylogenetic analysis revealed that OnTRAP5b is clustered with TRAP5b of teleost fish and shares a high amino acid sequence similarity with other TRAP5b in teleost fish (61.73-98.15%). Tissues expression analysis showed that OnTRAP5b was most abundant in the liver and was also widely expressed in other tissues. Upon challenge with
and
in vivo and in vitro, the expression of OnTRAP5b was significantly up-regulated. Additionally, the purified recombinant OnTRAP5b ((r)OnTRAP5) protein exhibited optimal phosphatase activity at pH 5.0 and an ideal temperature of 50 °C. The
,
and
of purified (r)OnTRAP5b were found to be 0.484 μmol × min
× mg
, 2.112 mM, and 0.27 s
with respect to
NPP as a substrate, respectively. Its phosphatase activity was differentially affected by metal ions (K
, Na
, Mg
, Ca
, Mn
, Cu
, Zn
, and Fe
) and inhibitors (sodium tartrate, sodium fluoride, and EDTA). Furthermore, (r)OnTRAP5b was found to promote the expression of inflammatory-related genes in head kidney macrophages and induce reactive oxygen expression and phagocytosis. Moreover, OnTRAP5b overexpression and knockdown had a significant effect on bacterial proliferation in vivo. When taken together, our findings suggest that OnTRAP5b plays a significant role in the immune response against bacterial infection in Nile tilapia.
Plasma cells are terminally differentiated antibody-secreting B lymphocytes that contribute to humoral immunity by producing large numbers of antibodies. Increasing evidence suggests that teleost ...fish B cells share certain characteristics with mammalian B1 B cells, including antibody-secreting, phagocytic, and antigen-presenting capacities. However, the difference between mature B cells and plasma cells remains unclear. In this study, we found that, based on their light-scattering characteristics, tilapia anterior kidney (AK) leukocytes can be categorized into two IgM
+
B-cell subsets: the lymphoid (L) gate and granulocyte–monocyte/macrophage (G-M) subsets. G-M gate cells are more numerous than L-gate cells and have higher mean fluorescence, but lower forward scatter and side scatter. We analyzed the morphological and ultrastructural features of sorted IgM
+
cells and found that L-gate IgM
+
cells have a high nucleus–cytoplasm ratio and lymphocyte-like morphology, whereas G-M gate IgM
+
cells have a small nucleus, more abundant endoplasmic reticulum, and a larger number of mitochondria, and have a plasma cell-like or macrophage-like morphology. To further characterize the cell types, we examined the specific patterns of expression of B-cell- and T-cell-related genes. We found that B-cell-specific genes were expressed by both L-gate and G-M gate IgM
+
cells, and that G-M gate IgM
+
cells secreted extremely high levels of IgM. However, T-cell-related genes were highly expressed only in L-gate IgM
–
cells. These results suggest that G-M gate IgM
+
cells are similar to plasma-like cells, with high antibody-secreting capacity. Given that G-M gate cells include the granulocyte, monocyte, and macrophage cell types, but not B cells, monocyte/macrophage markers were used to investigate the cell types further. A macrophage receptor with a collagenous structure was frequently observed, and macrophage-expressed gene-1 was highly expressed, in the G-M gate IgM
+
cells. Phagocytic capacity, as determined by ingestion of beads or bacteria, was significantly higher in G-M gate IgM
+
cells than in L-gate IgM
+
cells, as was antigen-processing capacity. Our findings show that tilapia AK leukocytes can be divided into two IgM
+
B-cell subsets and that G-M gate IgM
+
cells resemble plasma-like cells, having high antibody-secreting, phagocytic, and antigen-presenting capacities. Thus, this study increases our understanding of the functions of teleost fish plasma-like cells.
The heavy metal lead (Pb) is a contaminant widely distributed in the food chain. In this study, eight weeks of feeding containing Garlic (
Allium sativum
) or Fu-ling (
Poria cocos
) or both, ...markedly increased the growth index, enzyme activity, and serum index and significantly decreased muscle Pb level in grass carp (
Ctenopharyngodon idella
). Upon Pb exposure, the feeding Garlic or Fu-ling or both possessed the similar effects on improving the function of the antioxidant system and chelating ability. Further, the gene expressions of metal binding proteins (
TF
and
MT-2
) in the liver of the three experimental groups were significantly higher than those of the control group, which were all highly up-regulated after Pb exposure. At the same time, the activities of antioxidant enzymes (SOD and CAT) and the content of non-enzymatic substance (GSH) in the liver of the Garlic group, Fu-ling group and mixed group were stable compared to the control group after Pb exposure. Moreover, the reduction of Pb toxicity was manifested by the decrease of Pb content in the muscle, and the stable expression of heat stress proteins (
HSP30
and
HSP60
) and immune-related genes (
TNF-α
and
IL-1β
). Taken together, the study preliminarily shows that the Garlic and Fu-ling play a role in mitigating the toxicity of Pb in grass carp.
The bending vibration of transmission shafting directly influences dynamic performance of mechanical systems. The adoption of carbon fiber-reinforced plastics (CFRP) hollow shaft in the long-span ...transmission shafting can effectively reduce bending vibration. This paper aims to modify the transfer matrix method (TMM) for the CFRP/Steel composite transmission shafting system based on lamination theory and layer-wise beam theory. The dynamic kinetic equations of the steel and CFRP segments of the composite transmission shafting were modeled; then the bending vibration was solved by combining the boundary conditions of the CFRP/Steel composite transmission shafting. The experimental tests have been carried out in the CFRP/Steel composite transmission shafting to obtain the critical speed of rotation. Moreover, the results of modified TMM were compared with experimental tests, finite element method, and simply supported beam model. The comparison results show that the modified TMM proposed in this paper can effectively calculate the bending vibration characteristics of the CFRP/Steel composite transmission shafting system.
Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells ...locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3
CD4
CD8
, CD3
CD4
CD8
, CD4
CD8
, and CD4
CD8
T cells existed in AK, but neither CD4
CD8
nor CD4
CD8
T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4
CD8
and CD4
CD8
T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.
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