Abetting the enemy
Bai and colleagues 10 demonstrate that in a human myelomonocytic cell line THP-1 , Mtb-induced LC3II expression a marker of autophagic activation was significantly reduced by pretreatment with nicotine in a dose-dependent manner. Similarly, when compared with the medium-exposed controls, nicotine-exposed murine alveolar macrophages AMs exhibited significantly fewer autophagosomes and a concomitant increase in the intracellular Mtb burden.
These results collectively demonstrate that nicotine impairs macrophage anti-Mtb autophagy. However, the observed reduction in the number of autophagosomes in nicotine-pretreated, Mtb-infected macrophages is a deviation from previous non-Mtb studies in which CS exposure was found to decrease functional autophagy in AMs.
In that regard, despite a marked increase in the accumulation of autophagosomes, the AMs of smokers exhibited an autophagic defect manifested by decreased lysosomal delivery of bacteria Therefore, further studies are needed to determine whether this difference reflects a unique characteristic of anti-Mtb autophagy in macrophages or arises from the use of nicotine as opposed to CS extract. Bai and colleagues 10 also report that nicotine stimulates FoxP3 Treg cells.
Bai and colleagues 10 also found that Mtb induces Treg cells, which helps to establish infection by inhibiting the proliferation of T helper 1 Th1 , Th2, and Th17 cells, and skewing macrophage differentiation toward a deactivated M2 phenotype. Nevertheless, future investigations are needed to further define the molecular and cellular mechanisms by which nicotine-exposed Tregs increase the Mtb burden in macrophages through M2 polarization.
The nAChRs are the receptors for the cholinergic antiinflammatory pathway CAP , which maintains immune homeostasis with the help of effectors from the nervous system e. Inhibition of nAChR signaling by mecamylamine treatment or the use of gene-deficient mice partially abrogates the ability of CS extract to suppress the anti-Mtb defense of macrophages.
These results suggest a critical role for nAChR signaling in CS-mediated suppression of the macrophage defense against Mtb. However, a comprehensive analysis of possible ramifications associated with the involvement of the nAChR-CAP axis in CS-mediated suppression of the macrophage anti-Mtb defense is needed. Previous studies have shown that CS, a complex mixture of toxic and bioactive chemicals, abets respiratory pathogens by suppressing immune defenses and by augmenting bacterial virulence 12 , Although much is still to be revealed about the complex interplay between immune effectors and bacterial virulence factors in the presence of CS, with every new discovery we identify novel cellular and molecular effectors that potentially can be harnessed therapeutically to alleviate respiratory infections like TB in individuals exposed to CS.
However, additional studies are required to assess the effects of CS exposure on autophagy and Treg cell functions in smokers infected with Mtb. In conclusion, the current article shows that nicotine interacts with nAChR on the surface of macrophages and impairs their anti-Mtb defense by direct suppression of autophagosomal killing as well as indirect induction of immunosuppressive FoxP3 [Treg] cells mechanisms.
Establishing nicotine as an important immunomodulatory component of CS is highly relevant from a public health viewpoint because nicotine is the principal component of the e-liquid contained in the cartridges of various electronic nicotine delivery systems that are gaining in popularity among the youth in the United States Further studies are required to demonstrate whether other key components of CS, including acrolein and reactive oxygen intermediates, suppress anti-Mtb immunity in macrophages through similar mechanisms.
Thus, the data need to be validated in human and mouse primary macrophages. Future studies are also needed to determine whether nicotine regulates inhibition of phagosome-lysosome fusion or escape from the phagosome to the cytoplasm by Mtb. Although macrophages are critical for the immune defense against Mtb, the role of the nAChR-CAP axis in the anti-Mtb defense cannot be mediated solely by macrophages, as other myeloid and stromal cells reside in the lungs.
Finally, the in vitro findings need be replicated in an in vivo model using CS firsthand or secondhand to demonstrate their true clinical relevance. Footnotes Author disclosures are available with the text of this article at www. References 1. N Engl J Med. World Health Organization. Global tuberculosis report Exposure to second-hand smoke and the risk of tuberculosis in children and adults: a systematic review and meta-analysis of 18 observational studies.
PLoS Med. Smoking increases risk of recurrence after successful anti-tuberculosis treatment: a population-based study. Int J Tuberc Lung Dis. Arch Trading Company, Inc. The U. Despite arguments by the company that violation of the order was not an "offense" under federal law, the U.
Court of Appeals for the Fourth Circuit held that the company could be properly charged. United States v. Arch Trading Co. Further readings Bordwell, Percy. The Law of War between Belligerents. Littleton, Colo. Green, Leslie C. Essays on the Modern Law of War. Ardsley, N. Cross-references Rules of War ; War. West's Encyclopedia of American Law, edition 2.
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The truth is, she has suspected as much the day he brought the cash home, but has been reluctant to say something. Throughout the investigation, in this example of aiding and abetting, Della denies any involvement with, or even knowledge of the crime. History of Aiding and Abetting as a Crime In the United States, the first law dealing with the issue of holding someone responsible for assisting someone in the commission of a crime was passed in The law made it a crime to aid, counsel, advise, or command someone in the commission of a murder , or of robbery on land or sea, or of piracy at sea.
In , the law was expanded to include the commission of any felony. In , the law was done away with, and replaced with a more modern statute, now found in 18 U. Section The changes primarily include modernization of language and grammatical style. Section became 18 U. Section 2 a. This updated law makes it clear that someone who aids and abets the commission of a crime will be punished as though he or she did commit the crime. In a federal case, those elements include: The accused specifically intended to aid in the commission of the crime, for the purpose of making the endeavor successful; The accused took positive action to aid, or participated in some element of, the commission of the crime, though the level of participation may be relatively small; Someone other than the accused actually committed the underlying crime.
To gain a conviction, a jury must be convinced that the elements of aiding and abetting are present, beyond a reasonable doubt. In truth, once the prosecution establishes that the defendant knew about the crime, or the unlawful purpose of some element, it has made sufficient connection for the jury to convict. Differences Between Aiding and Abetting, and Accessory Both aiding and abetting, and acting as an accessory to a crime, are illegal acts.
Specific laws regarding these actions vary by jurisdiction , and the definitions overlap in some ways, leading to their interchangeable use. There are differences between aiding and abetting, and accessory, however. Aiding — the giving of assistance or support to someone else in their commission of a crime. Abetting — the encouragement, or motivating someone to commit a crime. This may include rabble-rousing, goading, and instigating someone, or a crowd, to commit an illegal act.
Accessory — a person who actually assists in the commission of a crime committed primarily by someone else. In most jurisdictions, the law distinguishes between an accessory after the fact, and an accessory before the fact, lending additional prosecutorial power. To be convicted of this type of crime, however, the prosecution must prove that the accomplice knew that a crime was being, or had been, committed by the principal.
What is Conspiracy The primary difference between aiding and abetting or being an accessory to a crime and a conspiracy is whether or not the crime was actually committed. While the former are charges imposed after the crime has been committed — naming a third party who helped in some way to facilitate or cover up the crime — someone can be charged with conspiracy, even if the crime never happened.
This is not to say that anyone who daydreams up a crime can be charged with conspiracy. If, however, two or more people collaborate on how to commit a specific crime, coming up with plans to carry it out, they have conspired to commit that crime. Should something happen to prevent them from engaging that plan, they still have committed the crime of conspiracy. For example: Armand, an executive assistant at a finance firm, knows that his boss keeps certain passwords and login information in a notebook in his desk drawer.
He befriends Letti, who he knows has no problem doing things that are morally questionable. Another employee overhears Armand and Letti talking over lunch on the patio, and mentions it to management, who calls the police. A quiet investigation ensued, with police interviewing witnesses, and viewing surveillance video of the pair talking frequently.
Both Armand and Letti are then taken into custody, and charged with conspiracy to commit the crime — even though the actual crime was never completed. Charges of harboring or protecting the enemy may be applicable if: the accused, without proper authority, harbored or protected a person; the person so harbored or protected was the enemy; and the accused knew that the person so harbored or protected was an enemy.
Giving intelligence to the enemy may be charged if: the accused, without proper authority, knowingly gave intelligence information to the enemy; and the intelligence information was true, or implied the truth, at least in part.
The service member may be charged with communicating with the enemy if: the accused, without proper authority, communicated, corresponded, or held intercourse with the enemy; and; the accused knew that the accused was communicating, corresponding, or holding intercourse with the enemy. Understanding Article b Aiding the Enemy of the UCMJ Aiding or attempting to aid the enemy refers to the transfer of arms, ammunition, supplies, money, etc. Harboring or protecting the enemy requires the enemy is shielded without proper authority and the accused knew the other party was an enemy.
Knowledge of the other party being an enemy may be proven through the use of circumstantial evidence. In order for giving intelligence to the enemy to be applicable, the information provided to the enemy must have been true or implied as true, the accused must have had knowledge the other party was an enemy, and the intelligence provided to the enemy was useful to the enemy. The intelligence may have been conveyed directly or indirectly.
Communicating with the enemy is the unauthorized communication, correspondence, or intercourse with the enemy. The intent, content, and method of communication, correspondence, or intercourse is irrelevant, and the offense is complete the moment the accused issues the communication, correspondence, or intercourse directly or indirectly.
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