Monophosphoryl lipid A directly regulates Th1 cytokine production in human CD4+ T-cells through Toll-like Receptor 2 and 4

Immunobiology ◽  
2021 ◽  
pp. 152132
Author(s):  
Mousa Komai-Koma ◽  
Yuan Ji ◽  
Hui Cao ◽  
Zhigang Liu ◽  
Charles McSharry ◽  
...  
2016 ◽  
Vol 7 ◽  
Author(s):  
Jaxaira Maggi ◽  
Katina Schinnerling ◽  
Bárbara Pesce ◽  
Catharien M. Hilkens ◽  
Diego Catalán ◽  
...  

2011 ◽  
Vol 79 (9) ◽  
pp. 3576-3587 ◽  
Author(s):  
Christopher D. Romero ◽  
Tushar K. Varma ◽  
Jason B. Hobbs ◽  
Aimee Reyes ◽  
Brandon Driver ◽  
...  

ABSTRACTMonophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that is currently used as a vaccine adjuvant in humans. In this study, we evaluated the effect of MPLA treatment on the innate immune response to systemic bacterial infections in mice. Mice treated with MPLA after burn injury showed improved survival and less local and systemic dissemination of bacteria in a model ofPseudomonas aeruginosaburn wound infection. Prophylactic treatment with MPLA significantly enhanced bacterial clearance at the site of infection and reduced systemic dissemination of bacteria despite causing attenuation of proinflammatory cytokine production during acute intra-abdominal infection caused by cecal ligation and puncture. Administration of MPLA at 1 h after CLP also improved bacterial clearance but did not alter cytokine production. MPLA treatment increased the numbers of granulocytes, double-positive myeloid cells, and macrophages at sites of infection and increased the percentage and total numbers of myeloid cells mediating phagocytosis of bacteria. Depletion of Ly6G+neutrophils, but not macrophages, eliminated the ability of MPLA treatment to improve bacterial clearance. The immunomodulatory effects of MPLA were absent in TLR4-deficient mice. In conclusion, these studies show that MPLA treatment significantly augments the innate immune response to bacterial infection by enhancing bacterial clearance despite the attenuation of proinflammatory cytokine production. The enhanced bacterial clearance is mediated, in part, by increased numbers of myeloid cells with effective phagocytic functions at sites of infection and is TLR4 dependent.


2020 ◽  
Vol 65 (3) ◽  
pp. 652-660
Author(s):  
Ibrahim Aly ◽  
Essam H. Ibrahim ◽  
Rabab S. Hamad ◽  
Hoda E. L. Sayed ◽  
Sama M. N. Attiyah ◽  
...  

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 633
Author(s):  
Woo Sik Kim ◽  
Yong Zhi ◽  
Huichen Guo ◽  
Eui-Baek Byun ◽  
Jae Hyang Lim ◽  
...  

Virus-like particles (VLPs) have emerged as promising vaccine candidates against foot-and-mouth disease (FMD). However, such vaccines provide a relatively low level of protection against FMD virus (FMDV) because of their poor immunogenicity. Therefore, it is necessary to design effective vaccine strategies that induce more potent immunogenicity. In order to investigate the means to improve FMD VLP vaccine (VLPFMDV) immunogenicity, we encapsulated VLPs (MPL/DDA-VLPFMDV) with cationic liposomes based on dimethyldioctadecylammonium bromide (DDA) and/or monophosphoryl lipid A (MPL, TLR4 agonist) as adjuvants. Unlike inactivated whole-cell vaccines, VLPFMDV were successfully encapsulated in this MPL/DDA system. We found that MPL/DDA-VLPFMDV could induce strong cell-mediated immune responses by inducing not only VLP-specific IFN-γ+CD4+ (Th1), IL-17A+CD4+ (Th17), and IFN-γ+CD8+ (activated CD8 response) T cells, but also the development of VLP-specific multifunctional CD4+ and CD8+ memory T cells co-expressing IFN-γ, TNF-α, and IL-2. In addition, the MPL/DDA-VLPFMDV vaccine markedly induced VLP-specific antibody titers; in particular, the vaccine induced greater Th1-predominant IgG responses than VLPFMDV only and DDA-VLPFMDV. These results are expected to provide important clues for the development of an effective VLPFMDV that can induce cellular and humoral immune responses, and address the limitations seen in current VLP vaccines for various diseases.


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