mSphere of Influence: Adenosine in Host Defense against Bacterial Pneumonia—Friend or Foe?

ABSTRACT Elsa N. Bou Ghanem works in the field of innate immune senescence, inflammation, and host defense. In this mSphere of Influence article, she reflects on how “Adenosine A2B receptor deficiency promotes host defenses against Gram-negative bacterial pneumonia” by Barletta et al. (K. E. Barletta, R. E. Cagnina, M. D. Burdick, J. Linden, and B. Mehrad, Am J Respir Crit Care Med 186:1044–1050, 2012, https://doi.org/10.1164/rccm.201204-0622OC) impacted her own work examining the role of the extracellular adenosine pathway in neutrophil responses and host defense against pneumococcal pneumonia.

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TRIM Proteins and Their Roles in Antiviral Host Defenses

Annual Review of Virology ◽

10.1146/annurev-virology-092917-043323 ◽

2018 ◽

Vol 5 (1) ◽

pp. 385-405 ◽

Cited By ~ 56

Author(s):

Michiel van Gent ◽

Konstantin M.J. Sparrer ◽

Michaela U. Gack

Keyword(s):

Host Defense ◽

Host Immunity ◽

Innate Immune ◽

Host Defenses ◽

E3 Ligases ◽

Cellular Processes ◽

Cytokine Responses ◽

Tripartite Motif ◽

Trim Proteins

Tripartite motif (TRIM) proteins are a versatile family of ubiquitin E3 ligases involved in a multitude of cellular processes. Studies in recent years have demonstrated that many TRIM proteins play central roles in the host defense against viral infection. While some TRIM proteins directly antagonize distinct steps in the viral life cycle, others regulate signal transduction pathways induced by innate immune sensors, thereby modulating antiviral cytokine responses. Furthermore, TRIM proteins have been implicated in virus-induced autophagy and autophagy-mediated viral clearance. Given the important role of TRIM proteins in antiviral restriction, it is not surprising that several viruses have evolved effective maneuvers to neutralize the antiviral action of specific TRIM proteins. Here, we describe the major antiviral mechanisms of TRIM proteins as well as viral strategies to escape TRIM-mediated host immunity.

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TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00415.2010 ◽

2012 ◽

Vol 302 (5) ◽

pp. L447-L454 ◽

Cited By ~ 41

Author(s):

Louis R. Standiford ◽

Theodore J. Standiford ◽

Michael J. Newstead ◽

Xianying Zeng ◽

Megan N. Ballinger ◽

...

Keyword(s):

Lung Injury ◽

Bacterial Pneumonia ◽

Lavage Fluid ◽

Alveolar Epithelial Cells ◽

Intratracheal Administration ◽

Bacterial Colony ◽

Gram Negative ◽

Gm Csf

Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4lps-d mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4lps-d mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4lps-d AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4lps-d mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

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Four Reasons to Consider a Novel Class of Innate Immune Molecules in the Oral Epithelium

Journal of Dental Research ◽

10.1177/154405910308201202 ◽

2003 ◽

Vol 82 (12) ◽

pp. 944-950 ◽

Cited By ~ 29

Author(s):

E.E. LeClair

Keyword(s):

Host Defense ◽

Innate Immune System ◽

Physiological Response ◽

Three Dimensional ◽

Innate Immune ◽

Oral Epithelium ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Defense Protein ◽

Lines Of Evidence

An expanding number of innate immune molecules occupy the “epithelial frontier”. This review introduces a recently recognized class of mammalian proteins with similarity to PLUNC (palate, lung and nasal epithelium clone), which is itself related to the host defense protein BPI (bactericidal/permeability-increasing protein). Four emerging lines of evidence unite the PLUNC-like proteins: conserved genetic structure, epithelial expression, three-dimensional protein similarity, and a physiological response to injury or inflammation. By analogy to known proteins of the innate immune system, an emerging hypothesis for this family is that they act as sensors of Gram-negative bacteria in the oral cavity, among other areas.

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Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria

Microbes and Infection ◽

10.1016/s1286-4579(01)01481-2 ◽

2001 ◽

Vol 3 (14-15) ◽

pp. 1213-1222 ◽

Cited By ~ 41

Author(s):

Marina A Freudenberg ◽

Thomas Merlin ◽

Marina Gumenscheimer ◽

Christoph Kalis ◽

Regine Landmann ◽

...

Keyword(s):

Immune Response ◽

Salmonella Typhimurium ◽

Innate Immune Response ◽

Innate Immune ◽

Gram Negative Bacteria ◽

Primary Target ◽

Gram Negative

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Role of Specialized Pro-Resolving Mediators in Modifying Host Defense and Decreasing Bacterial Virulence

Molecules ◽

10.3390/molecules26226970 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6970

Author(s):

Julianne M. Thornton ◽

Kingsley Yin

Keyword(s):

Host Defense ◽

Host Response ◽

Tissue Repair ◽

Defense Mechanisms ◽

Neutrophil Migration ◽

Bacterial Virulence ◽

Innate Immune ◽

Bioactive Fatty Acids ◽

Insight Into

Bacterial infection activates the innate immune system as part of the host’s defense against invading pathogens. Host response to bacterial pathogens includes leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria. An appropriate host response requires resolution. The resolution phase involves attenuation of neutrophil migration, neutrophil apoptosis, macrophage recruitment, increased phagocytosis, efferocytosis of apoptotic neutrophils, and tissue repair. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that were shown to be highly effective in promoting resolution of infectious inflammation and survival in several models of infection. In this review, we provide insight into the role of SPMs in active host defense mechanisms for bacterial clearance including a new mechanism of action in which an SPM acts directly to reduce bacterial virulence.

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Variable Sensitivity of Oral Isolates of Eikenella Corrodens to Serum Bactericidal Activity: Role of Antibody

Advances in Dental Research ◽

10.1177/08959374880020022501 ◽

1988 ◽

Vol 2 (2) ◽

pp. 346-353 ◽

Cited By ~ 6

Author(s):

C. Chen ◽

M.E. Wilson

Keyword(s):

Human Serum ◽

Host Defense ◽

Potential Role ◽

Reference Strain ◽

Alternative Pathway ◽

Immune Defense ◽

Classical Pathway ◽

Eikenella Corrodens ◽

Gram Negative

Eikenella corrodens is a facultatively anaerobic Gram-negative bacterium which is among the predominant cultivable microflora of periodontal lesions characterized by loss of attachment level. In the present study, we examined the potential role of complement-mediated killing in host defense against this periodontopathic organism. Seven clinical isolates obtained from human subgingival plaque and one reference strain of E. corrodens were characterized with respect to (a) susceptibility to the bactericidal properties of pooled human serum and (b) the role of the classical and/or alternative pathway(s) of complement in effecting killing of sensitive strains. Six strains, including the reference strain, were found to be variably serum-sensitive, exhibiting 1-12.5% survival after two hr of incubation in the presence of 20% pooled human serum. The remaining two isolates were serum-resistant. Both serum-resistant and serum-sensitive strains consumed complement via the classical pathway in normal but not in hypogammaglobulinemic serum, thus ruling out an antibody-independent mechanism of classical pathway activation. Four of six serum-sensitive strains exhibited little or no loss of viability following incubation with serum depleted of the classical pathway component Clq. One strain which was resistant to killing by normal human serum was, nevertheless, highly susceptible to complement-mediated killing in the presence of rabbit immune serum. Two additional serum-sensitive strains were killed, albeit to a lesser extent, in Clq-depleted serum, indicative of a role of the alternative pathway in killing of some serum-sensitive strains. These results indicate a potential role for complement-mediated killing in host defense against Gram-negative periodontal bacteria such as E. corrodens. However, the ultimate contribution of this immune defense mechanism may be defined, at least in part, by the presence of a humoral response to key bacterial membrane constituents.

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ROLE OF HOST DEFENSE PEPTIDES OF THE INNATE IMMUNE RESPONSE IN SEPSIS

Shock ◽

10.1097/shk.0b013e318160de11 ◽

2007 ◽

pp. 1 ◽

Cited By ~ 3

Author(s):

Tobias Hirsch ◽

Marie Metzig ◽

Andreas Niederbichler ◽

Hans-Ulrich Steinau ◽

Elof Eriksson ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Host Defense ◽

Innate Immune ◽

Host Defense Peptides ◽

Defense Peptides

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NF-κB-Inducing Kinase Regulates Selected Gene Expression in the Nod2 Signaling Pathway

Infection and Immunity ◽

10.1128/iai.74.4.2121-2127.2006 ◽

2006 ◽

Vol 74 (4) ◽

pp. 2121-2127 ◽

Cited By ~ 43

Author(s):

Qilin Pan ◽

Vladimir Kravchenko ◽

Alex Katz ◽

Shuang Huang ◽

Masayuki Ii ◽

...

Keyword(s):

Host Defense ◽

Innate Immune System ◽

Muramyl Dipeptide ◽

Innate Immune ◽

Host Responses ◽

Leucine Rich Repeat ◽

Wild Type ◽

Primary Explants ◽

Repeat Domain

ABSTRACT The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-κB pathway. It has been suggested through indirect studies that NF-κB-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK−/− mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense.

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