Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Abstract

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.

LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells

“…The ability of LL-37 to directly inhibit a number of viruses has been reviewed previously (Barlow et al, 2014b), with further activities found against Aichi virus A (Vilas Boas et al, 2017), human adenoviruses 8 and 19 (HAdV-8 and HAdV-19) (Gordon et al, 2005; Uchio et al, 2013), hepatitis C virus (HCV) (Matsumura et al, 2016), human papillomavirus 16 (HPV16) (Buck et al, 2006), human rhinovirus (HRV) (Findlay et al, 2017; Schögler et al, 2016; Sousa et al, 2017), and varicella zoster virus (VZV) (Crack et al, 2012). While LL-37 has only been measured at 0.5 μg/ml in saliva (Bachrach et al, 2006; Takeuchi et al, 2012) and 10 μg/ml in gingival crevicular fluid 29 , the actual physiological concentration may be much higher at sites closer to the oral epithelial cells themselves due to the diffusion of the peptides once released from cells.…”

Emerging Role of Immunosuppression in Diseases Induced by Micro- and Nano-Particles: Time to Revisit the Exclusive Inflammatory Scenario

“…Administration of titanium oxide nanoparticles or liposomes inhibited lymphocyte- and macrophage-related immune responses and increased susceptibility to tumor growth ( 117 , 129 ). Augmented viral and bacterial infections have also been observed after exposure to carbon nanoparticles ( 130 , 131 ).…”

Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37

“…The process, called citrullination, involves changing the positively charged arginine in LL37 to citrulline and thus changing its charge from positive to neutral. This effectively removes the mechanism by which LL37 is able to destroy viruses and bacteria (5,33). Additionally, neutralization of charge by citrullination is responsible for disabling its ability to dampen inflammatory responses to viral infections.…”