scholarly journals A controversial role of neutrophils in tuberculosis infection pathogenesis

2021 ◽  
Vol 11 (5) ◽  
pp. 809-819
Author(s):  
I. A. Linge ◽  
A. S. Apt
Keyword(s):  
T Cell Activation ◽  
Lung Tissue ◽  
Cell Activation ◽  
Medical Problem ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Tissue Destruction ◽  
Infectious Process ◽  
Dendritic Cell Migration

Tuberculosis (TB) continues to be an important and unresolved medical problem. About a quarter of mankind is infected with Mycobacterium tuberculosis, and about 5–10% of these people eventually develop TB. Macrophages and CD4+ T cells are considered the key cells providing defense against TB infection. The role of neutrophils in TB is less well defined. Neutrophils are short-lived granulocytes among first migrate into the infectious lung tissue and phagocy tose mycobacteria. On the one hand, there is evidence for protective role of neutrophils in TB released via anti-microbial peptides inhibiting mycobacterial growth, up-regulation of CD4+ T-cell activation, and dendritic cell migration in the lymph nodes. On the other hand, infection of genetically TB susceptible animals leads to an overwhelming lung neutrophil inflammation, development of necrotic granulomata, and a rapid death. Neutrophils act directly or indirectly on mycobacteria by different oxidative or other reactions including neutrophil extracellular traps (NETs) formation. Phagocytosis of mycobacteria by neutrophils is accompanied by the production of pro-inflammatory factors, thus making neutrophils active participants of inflammation in all stages of the infectious process. Finally, neutrophils die by apoptosis or necrosis. Necrosis of neutrophils, which is activated by reactive oxygen species, also prolongs the inflammation. In this way, there is strong evidence that neutrophils are the cells involved in the transition of infection to the terminal stage, participating in lung tissue destruction. Although neutrophils evolutionary developed many ways to resist pathogens, it is likely, that neutrophils do not possess sufficient anti-mycobactericidal capacities due to the development of many adaptations allowing mycobacteria to survive inside the neutrophils. Neutrophils effectively phagocytose but poorly kill mycobacteria, thus hiding bacilli from more efficient killers, macrophages, and playing the role of the “Trojan Horse”. In this review, we summarize the data on the involvement of neutrophils in TB inflammation. We discuss their ambiguous role in pathogenesis which depends upon mycobacterial virulence, host genetics, dynamics of migration to inflammatory foci, and persistence during initial and chronic stages of the infectious process.

scholarly journals Effects of CX3CL1 inhibition on murine bleomycin-induced interstitial pneumonia

2020 ◽  
Vol 18 ◽  
pp. 205873922095990
Author(s):  
Soichi Yamada ◽  
Shion Miyoshi ◽  
Junko Nishio ◽  
Satoshi Mizutani ◽  
Zento Yamada ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
T Cell Activation ◽  
Lung Tissue ◽  
Cell Activation ◽  
Immunohistochemical Analysis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Novel Therapy ◽  
Tissue Sections

Background: Treatment for interstitial pneumonia (IP) associated with collagen diseases has not been established. There is a need to elucidate the pathogenesis of IP and develop a novel therapy. We aimed to clarify the role of chemokine (C-X3-C motif) ligand 1 (CX3CL1, also known as fractalkine) in IP. Methods: Bleomycin (BLM) was intratracheally administered to C57BL/6 mice to induce IP. For treatment with control Ab or anti-CX3CL1 mAb, the mice were administered either Ab three times per week for 2 weeks from the day of BLM administration until euthanasia. Expressions of CX3CL1 and its unique receptor CX3CR1 in the lung tissue were examined by immunohistochemical analysis. Cellular infiltration and lung fibrosis were evaluated based on hematoxylin-eosin-staining and Sirius red staining of the lung tissue sections, respectively. Bronchoalveolar lavage fluid (BALF) cells were analyzed by flow cytometry. Results: CX3CL1 and CX3CR1 were strongly expressed in the lung tissue from mice with BLM-induced IP (BLM-IP). Treatment with anti-CX3CL1 mAb did not significantly alter inflammatory cell infiltration or fibrosis in the lung tissue. However, the number of M1-like macrophages in BALF was decreased and surface CD3 expression on T cells was increased by anti-CX3CL1 mAb treatment. Conclusions: Inhibition of CX3CL1 decreased inflammatory cells and may attenuate T cell activation in BALF. CX3CL1 inhibitor may have the potential to suppress the infiltration and activation of immune cells in IP.

scholarly journals The role of β2 integrin in dendritic cell migration during infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tarfa Altorki ◽  
Werner Muller ◽  
Andrew Brass ◽  
Sheena Cruickshank
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Leukocyte Adhesion ◽  
Trichuris Muris ◽  
Dendritic Cell Migration ◽  
And Function ◽  
Kinetics Of

Abstract Background Dendritic cells (DCs) play a key role in shaping T cell responses. To do this, DCs must be able to migrate to the site of the infection and the lymph nodes to prime T cells and initiate the appropriate immune response. Integrins such as β2 integrin play a key role in leukocyte adhesion, migration, and cell activation. However, the role of β2 integrin in DC migration and function in the context of infection-induced inflammation in the gut is not well understood. This study looked at the role of β2 integrin in DC migration and function during infection with the nematode worm Trichuris muris. Itgb2tm1Bay mice lacking functional β2 integrin and WT littermate controls were infected with T. muris and the response to infection and kinetics of the DC response was assessed. Results In infection, the lack of functional β2 integrin significantly reduced DC migration to the site of infection but not the lymph nodes. The lack of functional β2 integrin did not negatively impact T cell activation in response to T. muris infection. Conclusions This data suggests that β2 integrins are important in DC recruitment to the infection site potentially impacting the initiation of innate immunity but is dispensible for DC migration to lymph nodes and T cell priming in the context of T. muris infection.

Anti-Inflammatory and Immunostimulatory Activities of Astragalosides

2017 ◽  
Vol 45 (06) ◽  
pp. 1157-1167 ◽  
Author(s):  
Yan Qi ◽  
Feng Gao ◽  
Lifei Hou ◽  
Chunping Wan
Keyword(s):  
T Cell ◽  
Phosphatase Activity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tyrosine Phosphatase ◽  
Protective Role ◽  
Anti Inflammatory ◽  
Regulatory Effects ◽  
Cell Balance

Astragalus membranaceus (Fisch) Bge (Huang-Qi) is a well-known herbal medicine with tonic property and has been widely used to treat cancer and other immune disorders in China and Southeast Asia for thousands of years. Accumulating evidence suggests that Huang-Qi possesses both immune-boosting and anti-inflammatory/immune-regulatory effects clinically, leaving the mechanism elusive. Recently, we discovered that Astragaloside (ASI), a major active component of Huang-Qi, is able to increase CD45 phosphatase activity. In this paper, we reviewed the recent progress of ASIs in immunoregulatory and anti-inflammatory activities, including the induction of T-cell activation, regulation of effector/regulatory T-cell balance, enhancement of CD45 phosphatase activity, inhibition of pro-inflammatory cytokine and, NF-[Formula: see text]B pathway. Finally, we hypothesized that inducing interferon-[Formula: see text] (IFN-[Formula: see text]) activity by activating CD45 protein tyrosine phosphatase (PTPase) may be involved in the protective role of ASI in two contrary immune-associated diseases. These pharmacological properties highlight the traditional uses of Astragalus and provide a new direction for subsequent research and the clinical application of this traditional herbal.

scholarly journals Protective Role of β-arrestin2 in Colitis Through Modulation of T-cell Activation

2015 ◽  
Vol 21 (12) ◽  
pp. 2766-2777 ◽  
Author(s):  
Deepika Sharma ◽  
Ankit Malik ◽  
Michael D. Steury ◽  
Peter C. Lucas ◽  
Narayanan Parameswaran
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Protective Role

scholarly journals An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

2021 ◽  
Vol 22 (15) ◽  
pp. 7975
Author(s):  
Saioa Gómez-Zorita ◽  
Iñaki Milton-Laskibar ◽  
Laura García-Arellano ◽  
Marcela González ◽  
María P. Portillo
Keyword(s):  
Adipose Tissue ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Current Evidence ◽  
Disease Outcomes ◽  
Lower Activation ◽  
Two Factors ◽  
Obese Subjects ◽  
Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

scholarly journals Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 834
Author(s):  
Frederike A. Hartl ◽  
Jatuporn Ngoenkam ◽  
Esmeralda Beck-Garcia ◽  
Liz Cerqueira ◽  
Piyamaporn Wipa ◽  
...  
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cooperative Interaction ◽  
Tcr Signaling ◽  
Binding Motifs ◽  
Adaptive Immune

The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαβ heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling.

Sign in / Sign up

Export Citation Format

Share Document