Antivirulence Properties of an Antifreeze Protein

Heisig, Martin; Abraham, Nabil M.; Liu, Lei; Neelakanta, Girish; Mattessich, Sarah; Sultana, Hameeda; Shang, Zhengling; Ansari, Juliana M.; Killiam, Charlotte; Walker, Wendy; Cooley, Lynn; Flavell, Richard A.; Agaisse, Hervé; Fikrig, Erol

doi:10.1016/j.celrep.2014.12.003

Cited by 7 publications

(12 citation statements)

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“…We adjusted the timing of the first dose of imipenem/cilastatin from 1 to 6 h postoperative to maintain a mortality rate of 30-60% throughout the duration of the study. For the experiment comparing C57BL/6J, IRF3-KO (original), and IRF3-KO (backcrossed) mice, we used the severe model of sepsis described in our prior studies (21,(23)(24)(25).…”

Section: Sepsis Modelmentioning

confidence: 99%

“…A genome scan revealed that the backcrossed mice were 96.9% congenic to C57BL/6J strain. To get an expedient answer using the minimum number of animals, we performed the severe CLP model described in our prior reports (21,(23)(24)(25). We induced severe CLP in the IRF3-KO (backcrossed) mice alongside the IRF3-KO (original) mice and C57BL/6J controls.…”

Section: An Irf3-deficient Host Environment Attenuates Il-6 Production By Adoptively Transferred Monocytesmentioning

confidence: 99%

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IRF3 Signaling within the Mouse Stroma Influences Sepsis Pathogenesis

Heipertz

Harper

Goswami

et al. 2021

The Journal of Immunology

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IFN regulatory factor 3 (IRF3) is a transcription factor that is activated by multiple pattern-recognition receptors. We demonstrated previously that IRF3 plays a detrimental role in a severe mouse model of sepsis, induced by cecal ligation and puncture. In this study, we found that IRF3-knockout (KO) mice were greatly protected from sepsis in a clinically relevant version of the cecal ligation and puncture model incorporating crystalloid fluids and antibiotics, exhibiting improved survival, reduced disease score, lower levels of serum cytokines, and improved phagocytic function relative to wild-type (WT) mice. Computational modeling revealed that the overall complexity of the systemic inflammatory/immune network was similar in IRF3-KO versus WT septic mice, although the tempo of connectivity differed. Furthermore, the mediators driving the network differed: TNF-a, IL-1b, and IL-6 predominated in WT mice, whereas MCP-1 and IL-6 predominated in IRF3-KO mice. Network analysis also suggested differential IL-6-related inflammatory programs in WT versus IRF3-KO mice. We created bone marrow chimeras to test the role of IRF3 within leukocytes versus stroma. Surprisingly, chimeras with IRF3-KO bone marrow showed little protection from sepsis, whereas chimeras with IRF3-KO stroma showed a substantial degree of protection. We found that WT and IRF3-KO macrophages had a similar capacity to produce IL-6 and phagocytose bacteria in vitro. Adoptive transfer experiments demonstrated that the genotype of the host environment affected the capacity of monocytes to produce IL-6 during sepsis. Thus, IRF3 acts principally within the stromal compartment to exacerbate sepsis pathogenesis via differential impacts on IL-6-related inflammatory programs.

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Section: Sepsis Modelmentioning

confidence: 99%

Section: An Irf3-deficient Host Environment Attenuates Il-6 Production By Adoptively Transferred Monocytesmentioning

confidence: 99%

IRF3 Signaling within the Mouse Stroma Influences Sepsis Pathogenesis

Heipertz

Harper

Goswami

et al. 2021

The Journal of Immunology

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“…A la fecha, no es claro cómo la bacteria penetra y coloniza el intestino medio de la garrapata, ni mucho menos, los mecanismos moleculares asociados. Sin embargo, se ha demostrado que la glicoproteína anticoagulante IAFGP de I. scapularis, es capaz de inhibir la formación de las biopelículas bacterianas (Heisig et al, 2014). Interesantemente, la bacteria A. phagocytophilum, secuestra a la proteína IAFGP, con el fin de alterar su acumulación en el intestino medio de las garrapatas para inhibir el desarrollo de biopelículas, permitiendo así su colonización y establecimiento en el vector (Heisig et al, 2014).…”

Section: Estudio Del Microbioma En Garrapatasunclassified

Avance en el estudio del microbioma de garrapatas: una visión hologenómica en busca de nuevas estrategias para su control

Aguilar-Díaz

Quiroz-Castañeda

Castro-Saines

et al. 2021

RECEIN

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Las garrapatas son ectoparásitos hematófagos que transmiten diversos agentes infecciosos, incluyendo bacterias que afectan al ser humano y otros animales, y cuyas enfermedades generan pérdidas económicas importantes. Sin embargo, aún permanecen sin esclarecerse los mecanismos en los que están involucrados la microbiota de las garrapatas y el patógeno en el vector durante el proceso de transmisión. Actualmente, sabemos que los artrópodos son capaces de albergar una gran biodiversidad de microorganismos como bacterias, protozoarios, hongos y virus, y que éstos, desempeñan funciones fundamentales en el establecimiento, reproducción, fisiología, nutrición, y probablemente también con la capacidad vectorial. En este sentido, la relación patógeno-microbiota, representa una caja negra de interacciones que podrían acercarnos más a la elucidación y comprensión de las enfermedades transmitidas por vectores. Al momento, diversos estudios Metagenómicos han sido utilizados para la caracterización del microbioma de diferentes hospederos, y más recientemente de muchos vectores artrópodos de importancia médico-veterinaria. No obstante, poco se sabe acerca de la influencia de la microbiota sobre la capacidad vectorial, lo cual, resulta de suma importancia para comprender mejor la relación hologenómica que guardan los vectores con los patógenos que transmite, e incluso con las bacterias no patógenas que poseen. La elucidación de las relaciones biológicas entre los microorganismos presentes en las garrapatas, los patógenos y no patógenos que transmite y su hospedero, proporcionará información invaluable, que contribuya al desarrollo de estrategias novedosas de control de plagas de artrópodos y patógenos transmitidos por vectores.

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“…Microbial biofilms (6), generated by diverse bacterial species, are essential for bacterial colonization microbiota favoring the abundance of strong biofilm formers. Results demonstrate that communities of bacteria are functionally redundant, suggesting a mechanism by ticks selecting the adequate microbiome fulfilling a core set of functions.…”

Section: Introductionmentioning

confidence: 99%

Resistance of tick microbiome to biological disturbance

Estrada-Peña¹,

Cabezas‐Cruz²,

Obregón³

2019

Preprint

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Background : Ixodes scapularis ticks harbor microbial communities including pathogenic and non-pathogenic microbes. Pathogen infection increases the expression of several tick gut proteins which disturb the tick gut microbiota and impact bacterial biofilm formation. Anaplasma phagocytophilum induces ticks to express I. scapularis IAFGP, a protein with antimicrobial activity while Borrelia burgdorferi induces the expression of PIXR. Here, we tested the resistance of I. scapularis microbiome to A. phagocytophilum infection, antimicrobial peptide IAFGP, and anti-tick immunity specific to PIXR. Results : We demonstrate that A. phagocytophilum infection and IAFGP affect the taxonomic composition and taxa co-occurrence networks but had no effect on the functional traits of tick microbiome. In contrast, anti-tick immunity disturbed the taxonomic composition and the functional profile of tick microbiome, by increasing both taxonomic and pathways diversity. Mechanistically, we show that anti-tick immunity increases the representation and importance of polysaccharide biosynthesis pathways involved in biofilm formation while these pathways are under-represented in the microbiome of ticks infected by A. phagocytophilum or exposed to IAFGP. Conclusions : These analyses revealed that tick microbiota is highly sensitive to anti-tick immunity, while it is less sensitive to pathogen infection and antimicrobial peptides. Results suggest that biofilm formation is a defensive response of tick microbiome to anti-tick immunity.

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Antivirulence Properties of an Antifreeze Protein

Cited by 7 publications

References 0 publications

IRF3 Signaling within the Mouse Stroma Influences Sepsis Pathogenesis

IRF3 Signaling within the Mouse Stroma Influences Sepsis Pathogenesis

Avance en el estudio del microbioma de garrapatas: una visión hologenómica en busca de nuevas estrategias para su control

Resistance of tick microbiome to biological disturbance

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