Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization

Huggins, Matthew A; Sjaastad, Frances V.; Pierson, Mark; Kucaba, Tamara A.; Swanson, Whitney; Staley, Christopher; Weingarden, Alexa R.; Jensen, Isaac J.; Danahy, Derek B.; Badovinac, Vladimir P.; Jameson, Stephen C.; Vezys, Vaiva; Masopust, David; Khoruts, Alexander; Griffith, Thomas S.; Hamilton, Sara E.

doi:10.1016/j.celrep.2019.07.028

Cited by 79 publications

(136 citation statements)

References 92 publications

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“…Although formal evidence of training is absent, macaque neutrophils were recently reported to express higher levels of CD11b, TNF-a, IL-21, MPO, and ROS 2 weeks after a second mucosal immunization with a replication-competent adenovirus-SIV recombinant than before any immunization 43 . After physiological microbial exposure of laboratory mice by cohousing with pet store mice, TLR4 + monocyte, TLR2 + monocyte, and TLR2 + neutrophil counts increased 44 . Additionally, training of DCs was recently reported.…”

Section: Discussionmentioning

confidence: 95%

Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

et al. 2020

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Comprehending the mechanisms behind the impact of vaccine regimens on immunity is critical for improving vaccines. Indeed, the time-interval between immunizations may influence B and T cells, as well as innate responses. We compared two vaccine schedules using cynomolgus macaques immunized with an attenuated vaccinia virus. Two subcutaneous injections 2 weeks apart led to an impaired secondary antibody response and similar innate myeloid responses to both immunizations. In contrast, a delayed boost (2 months) improved the quality of the antibody response and involved more activated/mature innate cells, induced late after the prime and responding to the recall. The magnitude and quality of the secondary antibody response correlated with the abundance of these neutrophils, monocytes, and dendritic cells that were modified phenotypically and enriched prior to revaccination at 2 months, but not 2 weeks. These late phenotypic modifications were associated with an enhanced ex vivo cytokine production (including IL-12/23 and IL-1β) by PBMCs short after the second immunization, linking phenotype and functions. This integrated analysis reveals a deep impact of the timing between immunizations, and highlights the importance of early but also late innate responses involving phenotypical changes, in shaping humoral immunity.npj Vaccines (2020) 5:24 ; https://doi.

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Section: Discussionmentioning

confidence: 95%

Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

et al. 2020

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“…Additionally, it was reported that the activation of TLR4 signaling pathways play a vital role in virus induced in ammatory response and subsequent cytokine storm, thus leading to severe ALI, ARDS (acute respiratory distress syndrome), MODS and even death [58][59][60]. Currently, the eruptible corona virus disease 19 (COVID 19), as a new coronavirus pneumonia with rapid infectiousness and great hazard, is also an infectious disease of the lungs [61].…”

Section: Discussionmentioning

confidence: 99%

YiQiFuMai Lyophilized Injection Attenuates Sepsis-Induced Acute Lung Injury via TLR4/Src/VE-cadherin/p120-catenin Signaling Pathway

Pan¹,

Xue²,

Zhou³

et al. 2020

Preprint

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Background: Sepsis is a severe disorder leading to a clinically critical syndrome of multiple organ dysfunction syndrome. Most patients with sepsis will be associated with acute lung injury (ALI), which is an independent risk factors of organ failure and death in patients with sepsis at the same time. YiQiFuMai Lyophilized Injection (YQFM) is a modern traditional Chinese prescription preparation, which could ameliorate ALI induced by lipopolysaccharide (LPS) or fine particulate matter. The current study aimed to investigate the effect of YQFM on sepsis-induced ALI and the underlying mechanism.Methods: Male C57BL/6J mice were treated with cecal ligation and puncture (CLP) after tail intravenous injected with YQFM (1, 2 and 4 g/kg). The measurements of lung edema, evans blue leakage, myeloperoxidase content, inflammatory cells in bronchoalveolar lavage fluid, histopathological assay and expression of associated proteins were performed at 18 h after CLP.Results: The results illustrated that YQFM inhibited pulmonary edema and inflammatory response, thus ameliorated ALI in sepsis mice. Furthermore, the expression of TLR4 and phosphorylated Src was down-regulated, and the expression of p120-catenin and VE-cadherin was restored by YQFM administration.Conclusion: Our study suggested the therapeutic potential of YQFM on treating sepsis-induced ALI via regulating TLR4/Src/VE-cadherin/p120-catenin signaling pathway.

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“…When exposed to low virulence Listeria monocytogenes that interacts with TLR2, CoH showed enhanced immune responses allowing better survival than SPF mice. The opposite took place when these mice were exposed to peritoneal sepsis mediated through cytokine storm 11 . In other terms, tolerance through TLR2 interaction is mostly favored in a setting of chronic well-tolerated infection.…”

Section: Figure 2 Production Of Tumour Necrosis Factor-alpha By the mentioning

confidence: 99%

Staphylococcus Aureus Osteomyelitis as an Inducer of Tolerance to Escherichia Coli Pyelonephritis: an Experimental Study

Goumenos

Savvidou

Renieris

et al. 2020

Sci Rep

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the high incidence of osteomyelitis in vulnerable populations like those with multiple injuries or elderly undergoing joint arthroplasties generates the question what may be their responses to subsequent infection by high virulent isolates. Rabbits were subject to two operations at three week intervals; sham osteomyelitis and sham pyelonephritis (group S); sham osteomyelitis and Escherichia coli pyelonephritis (group p); and Staphylococcus aureus osteomyelitis and E. coli pyelonephritis (group op). Survival was recorded; cytokine stimulation of circulating mononuclear cells (pBMcs) and tissue myeloperoxidase (Mpo) activity and bacterial growth were monitored. in some experiments, dalbavancin treatment was given before pyelonephritis. Healthy pBMcs were pre-treated with bone homogenate, S. aureus or both. Mortality of groups S, P and OP after induction of pyelonephritis was 0%, 50% and 8.3% respectively. tumour necrosis factor-alpha (tnfα) production by PBMCs was significantly lower in the OP group at 48 hours. E. coli bacterial load was similar in groups P and OP at death or sacrifice whereas the Mpo activity of group op was decreased. production of tnfα was further decreased among dalbavancin treated rabbits; in these rabbits tissue Mpo was increased. tnfα production decreased when healthy pBMcs pre-treated with bone homogenate, S. aureus (HKSA) or both were stimulated with E. coli (HKEC); production was further decreased in the presence of anti-TLR4 and anti-TLR9. It is concluded that staphylococcal osteomyelitis modulated the innate immune responses of the host leading to protection from death by highly virulent E. coli. tolerance to tLR ligands is the most likely mechanism of action.

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Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization

Cited by 79 publications

References 92 publications

Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

YiQiFuMai Lyophilized Injection Attenuates Sepsis-Induced Acute Lung Injury via TLR4/Src/VE-cadherin/p120-catenin Signaling Pathway

Staphylococcus Aureus Osteomyelitis as an Inducer of Tolerance to Escherichia Coli Pyelonephritis: an Experimental Study

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