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  This is an Open Access Journal Open Access journal
ISSN (Online) 2573-7732
Published by American Assoc of Immunologists Homepage  [2 journals]
  • FliCs Hypervariable D3 Domain Is Required for Robust Anti-Flagellin
           Primary Antibody Responses

    • Authors: Lopez-Yglesias, A. H; Lu, C.-C, Zhao, X, Chou, T, VandenBos, T, Strong, R. K, Smith, K. D.
      Pages: 422 - 432
      Abstract: Bacterial flagellin is a well-known agonist of the innate immune system that induces proinflammatory responses through the TLR5 and Naip5/6 recognition pathways. Several clinical trials investigating flagellin fusion proteins have demonstrated promising results for inducing protective immunity toward influenza virus, which has been largely attributed to flagellin’s ability to activate TLR5. Our laboratory previously demonstrated that the Salmonella enterica serovar Typhimurium flagellin protein, FliC, induces Ab responses in mice through a third pathway that is independent of TLR5, Casp1/11, and MyD88. In this study, we further define the structural features of FliC that contribute to this unknown third pathway. By destroying the Naip5/6 and TLR5 recognition sites, we demonstrate that neither were required for the TLR5-, inflammasome- and MyD88-independent Ab responses toward FliC. In contrast, deletion of FliC’s D3 or D0/D1 domains eliminated primary anti-flagellin Ab responses. For optimal primary and secondary anti-flagellin Ab responses we show that TLR5, inflammasome recognition, and the D3 domain of FliC are essential for flagellin’s robust immunogenicity. Our data demonstrate that the D3 domain of FliC influences immunogenicity independent of the known innate recognition sites in the D0/D1 domains to augment Ab production. Our results suggest full-length FliC is critical for optimal immunogenicity and Ab responses in flagellin-based vaccines.
      PubDate: 2019-09-05T07:16:35-07:00
      DOI: 10.4049/immunohorizons.1800061
      Issue No: Vol. 3, No. 9 (2019)
  • T Cell Metabolism Is Dependent on Anatomical Location within the Lung

    • Authors: Roberts, L. M; Evans, T. J, Bosio, C. M.
      Pages: 433 - 439
      Abstract: The metabolic shift from oxidative phosphorylation to glycolysis is universally accepted as a necessary step for immune cells to mount effector functions. However, it is unknown if this paradigm holds true for T cells regardless of anatomical location. In this study, we compared metabolic responses among distinct mouse pulmonary CD4+ effector T cell (Teff) pools following intranasal vaccination with either Francisella tularensis or Bordetella pertussis. Surprisingly, in contrast to circulating CD4+ Teff, upon ex vivo stimulation, resident CD4+ Teff did not shift to glycolysis. This impairment in the resident pool was modestly overcome following in vivo infection. However, consistent with an ex vivo triggered shift toward glycolysis, circulating CD4+ Teff remained superior compared with resident CD4+ Teff after in vivo infection. These data indicate differences in lung T cell metabolism is associated with anatomic location, a feature which may be exploited to enhance or dampen pulmonary T cell responses.
      PubDate: 2019-09-13T05:31:32-07:00
      DOI: 10.4049/immunohorizons.1900063
      Issue No: Vol. 3, No. 9 (2019)
  • Protection from Endotoxin Shock by Selective Targeting of Proinflammatory
           Signaling to the Nucleus Mediated by Importin Alpha 5

    • Authors: Liu, Y; Veach, R. A, Zienkiewicz, J, Boyd, K. L, Smith, T. E, Xu, Z.-Q, Wylezinski, L. S, Hawiger, J.
      Pages: 440 - 446
      Abstract: Endotoxin shock is induced by LPS, one of the most potent virulence factors of the Gram-negative bacteria that cause sepsis. It remains unknown if either proinflammatory stress-responsive transcription factors (SRTFs), ferried to nucleus by importin α5, or lipid-regulating sterol regulatory element binding proteins (SREBPs), transported to the nucleus by importin β1, mediate endotoxin shock. A novel cell-penetrating peptide targeting importin α5 while sparing importin β1 protected 80% of animals from death in response to a high dose of LPS. This peptide suppresses inflammatory mediators, liver glycogen depletion, endothelial injury, neutrophil trafficking, and apoptosis caused by LPS. In d-galactosamine–pretreated mice challenged by 700-times lower dose of LPS, rapid death through massive apoptosis and hemorrhagic necrosis of the liver was also averted by the importin α5–selective peptide. Thus, using a new tool for selective suppression of nuclear transport, we demonstrate that SRTFs, rather than SREBPs, mediate endotoxin shock.
      PubDate: 2019-09-18T08:56:33-07:00
      DOI: 10.4049/immunohorizons.1900064
      Issue No: Vol. 3, No. 9 (2019)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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