Muscovy duck reovirus infection rapidly activates host innate immune signaling and induces an effective antiviral immune response involving critical interferons

Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.

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Modulation of innate immune signaling by aCoxiella burnetiieukaryotic-like effector protein

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914892117 ◽

2020 ◽

Vol 117 (24) ◽

pp. 13708-13718 ◽

Cited By ~ 1

Author(s):

Melanie Burette ◽

Julie Allombert ◽

Karine Lambou ◽

Ghizlane Maarifi ◽

Sébastien Nisole ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Q Fever ◽

Effector Proteins ◽

Innate Immune ◽

Pcr Analysis ◽

Nuclear Fraction ◽

Nucleotide Exchange ◽

Immune Signaling ◽

Innate Immune Signaling

The Q fever agentCoxiella burnetiiuses a defect in organelle trafficking/intracellular multiplication (Dot/Icm) type 4b secretion system (T4SS) to silence the host innate immune response during infection. By investigatingC. burnetiieffector proteins containing eukaryotic-like domains, here we identify NopA (nucleolar protein A), which displays four regulator of chromosome condensation (RCC) repeats, homologous to those found in the eukaryotic Ras-related nuclear protein (Ran) guanine nucleotide exchange factor (GEF) RCC1. Accordingly, NopA is found associated with the chromatin nuclear fraction of cells and uses the RCC-like domain to interact with Ran. Interestingly, NopA triggers an accumulation of Ran-GTP, which accumulates at nucleoli of transfected or infected cells, thus perturbing the nuclear import of transcription factors of the innate immune signaling pathway. Accordingly, qRT-PCR analysis on a panel of cytokines shows that cells exposed to theC. burnetii nopA::Tn or a Dot/Icm-defectivedotA::Tn mutant strain present a functional innate immune response, as opposed to cells exposed to wild-typeC. burnetiior the correspondingnopAcomplemented strain. Thus, NopA is an important regulator of the innate immune response allowingCoxiellato behave as a stealth pathogen.

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Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei

Microbial Pathogenesis ◽

10.1016/j.micpath.2014.11.009 ◽

2015 ◽

Vol 78 ◽

pp. 20-28 ◽

Cited By ~ 6

Author(s):

Shahabuddin Alam ◽

Kei Amemiya ◽

Robert C. Bernhards ◽

Robert G. Ulrich ◽

David M. Waag ◽

...

Keyword(s):

Immune Response ◽

Nonhuman Primate ◽

Cellular Immune Response ◽

Mononuclear Cells ◽

Innate Immune ◽

Burkholderia Mallei ◽

Immune Signaling ◽

Innate Immune Signaling ◽

Cellular Immune

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Chronic immune response dysregulation in MDS pathogenesis

Blood ◽

10.1182/blood-2018-03-784116 ◽

2018 ◽

Vol 132 (15) ◽

pp. 1553-1560 ◽

Cited By ~ 43

Author(s):

Laura Barreyro ◽

Timothy M. Chlon ◽

Daniel T. Starczynowski

Keyword(s):

Immune Response ◽

Innate Immune ◽

Direct Role ◽

Immune Signaling ◽

Innate Immune Signaling ◽

Pathway Activation ◽

Immune Pathway ◽

Innate Immune Pathway ◽

Inflammatory Component

Abstract Chronic innate immune signaling in hematopoietic cells is widely described in myelodysplastic syndromes (MDS), and innate immune pathway activation, predominantly via pattern recognition receptors, increases the risk of developing MDS. An inflammatory component to MDS has been reported for many years, but only recently has evidence supported a more direct role of chronic innate immune signaling and associated inflammatory pathways in the pathogenesis of MDS. Here we review recent findings and discuss relevant questions related to chronic immune response dysregulation in MDS.

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