scholarly journals Granulocyte/Macrophage Colony-Stimulating Factor-Derived Macrophages Exhibit Distinctive Early Immune Response to Lymphocytic Choriomeningitis Virus Infection

2020 ◽  
Vol 33 (6) ◽  
pp. 477-488 ◽  
Author(s):  
Torki Alothaimeen ◽  
Kyle Seaver ◽  
Rylend Mulder ◽  
Katrina Gee ◽  
Sameh Basta
2003 ◽  
Vol 31 (10) ◽  
pp. 2462-2469 ◽  
Author(s):  
Sascha Flohé ◽  
Sven Lendemans ◽  
Christian Selbach ◽  
Christian Waydhas ◽  
Marcus Ackermann ◽  
...  

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3730-3736 ◽  
Author(s):  
Hsin-Ming Liu ◽  
Sally E. Newbrough ◽  
Sudershan K. Bhatia ◽  
Christopher E. Dahle ◽  
Arthur M. Krieg ◽  
...  

Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor (GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13 murine lymphoma system to evaluate the immune response to a combination of these two adjuvants. Immunization using antigen, CpG ODN, and soluble GM-CSF enhanced production of antigen-specific antibody and shifted production towards the IgG2a isotype, suggesting an enhanced TH1 response. This effect was most pronounced after repeat immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days before tumor inoculation prevented tumor growth. CpG ODN enhanced the production of interleukin-12 by bone marrow-derived dendritic cells and increased expression of major histocompatibility complex class I and class II molecules, particularly when cells were pulsed with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN in combination with strategies involving GM-CSF enhances the immune response to antigen and shifts the response towards a TH1 response and that this approach deserves further evaluation in tumor immunization approaches and other conditions in which an antigen-specific TH1 response is desirable.


Author(s):  
Torki Alothaimeen ◽  
Evan Trus ◽  
Sameh Basta ◽  
Katrina Gee

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) play an important role in macrophage (MФ) development by influencing their differentiation and polarization. Our goal was to explore the difference between M-CSF- and GM-CSF-derived bone marrow MФ responsiveness to TLR7-mediated signalling pathways that influence cytokine production early after infection in a model of acute virus infection. To do so, we examined cytokine production and TLR7-mediated signalling at 1 h post-lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) infection. We found that R848-induced cytokine expression was enhanced in these cells, with GM-CSF cells exhibiting higher proinflammatory cytokine expression and M-CSF cells exhibiting higher anti-inflammatory cytokine expression. However, R848-mediated signalling molecule activation was diminished in LCMV-infected M-CSF and GM-CSF macrophages. Interestingly, we observed that TLR7 expression was maintained during LCMV infection of M-CSF and GM-CSF cells. Moreover, TLR7 expression was significantly higher in M-CSF cells compared to GM-CSF cells. Taken together, our data demonstrate that although LCMV restrains early TLR7-mediated signalling, it primes differentiated MФ to enhance expression of their respective cytokine profiles and maintains levels of TLR7 expression early after infection.


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