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Host defense peptides, also known as antimicrobial peptides, are key elements of innate host defense. One host defense peptide with well-characterized antimicrobial activity is the human cathelicidin, LL-37. LL-37 has been shown to be upregulated at sites of infection and inflammation and is regarded as one of the primary innate defense molecules against bacterial and viral infection. Human exposure to combustion-derived or engineered nanoparticles is of increasing concern, and the implications of nanomaterial exposure on the human immune response is poorly understood. However, it is widely acknowledged that nanoparticles can interact strongly with several immune proteins of biological significance, with these interactions resulting in structural and functional changes of the proteins involved. This study investigated whether the potent antibacterial and antiviral functions of LL-37 were inhibited by exposure to, and interaction with, carbon nanoparticles, together with characterizing the nature of the interaction. LL-37 was exposed to carbon black nanoparticles in vitro, and the antibacterial and antiviral functions of the peptide were subsequently assessed. We demonstrate a substantial loss of antimicrobial function when the peptide was exposed to low concentrations of nanomaterials, and we further show that the nanomaterial-peptide interaction resulted in a significant change in the structure of the peptide. The human health implications of these findings are significant, as, to our knowledge, this is the first evidence that nanoparticles can alter host defense peptide structure and function, indicating a new role for nanoparticle exposure in increased disease susceptibility., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of literature to direct physicians in the prescribing of immunomodulators for patients with severe atopic dermatitis (AD)., Objective: To survey systemic agent prescribing practices for severe childhood AD among clinicians in the United States and Canada., Methods: The TREatment of severe Atopic dermatitis in children Taskforce (TREAT), US&CANADA, a project of the Pediatric Dermatology Research Alliance (PeDRA), developed an online multiple-response survey to assess clinical practice, gather demographic information and details of systemic agent selection, and identify barriers to their use in patients with recalcitrant pediatric AD., Results: In total, 133 of 290 members (45.9%) of the Society for Pediatric Dermatology completed the survey, and 115 of 133 (86.5%) used systemic treatment for severe pediatric AD. First-line drugs of choice were cyclosporine (45.2%), methotrexate (29.6%), and mycophenolate mofetil (13.0%). The most commonly used second-line agents were methotrexate (31.3%) and mycophenolate mofetil (30.4%); azathioprine was the most commonly cited third-line agent. The main factors that discouraged use of systemic agents were side-effect profiles (82.6%) and perceived risks of long-term toxicity (81.7%)., Limitations: Investigation of the sequence of systemic medications or combination systemic therapy was limited. Recall bias may have affected the results., Conclusion: Great variation exists in prescribing practices among American and Canadian physicians using systemic agents for treatment of pediatric AD., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required.

The potential toxicity of carbon nanotubes (CNTs) has been compared to pathogenic fibres such as asbestos. It is important to test this hypothesis to ascertain safe methods for CNT production, handling and disposal. In this study aspects reported to contribute to CNT toxicity were assessed: length, aspect ratio, iron content and crystallinity; with responses compared to industrially produced MWCNTs and toxicologically relevant materials such as asbestos. The impacts of these particles on a range of macrophage models in vitro were assessed due to the key role of macrophages in particle clearance and particle/fibre-induced disease. Industrially produced and long MWCNTs were cytotoxic to cells, and were potent in inducing pro-inflammatory and pro-fibrotic immune responses. Short CNTs did not induce any cytotoxicity. Frustrated phagocytosis was most evident in response to long CNTs, as was respiratory burst and reduction in phagocytic ability. Short CNTs, metal content and crystallinity had less or no influence on these endpoints, suggesting that many responses were fibre-length dependent. This study demonstrates that CNTs are potentially pathogenic, as they were routinely found to induce detrimental responses in macrophages greater than those induced by asbestos at the same mass-based dose., (Copyright © 2015 Elsevier Ltd. All rights reserved.)