The Role of the SARS-CoV-2 S-Protein Glycosylation in the Interaction of SARS-CoV-2/ACE2 and Immunological Responses.

The current pandemic is caused by the coronavirus disease 2019 (COVID-19), which is, in turn, induced by a novel coronavirus (SARS-CoV-2) that triggers an acute respiratory disease. In recent years, the emergence of SARS-CoV-2 is the third highly pathogenic event and large-scale epidemic affecting the human population. It follows the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. This novel SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor, like SARS-CoV, and spreads principally in the respiratory tract. The viral spike (S) protein of coronaviruses facilities the attachment to the cellular receptor, entrance, and membrane fusion. The S protein is a glycoprotein and is critical to elicit an immune response. Glycosylation is a biologically significant post-translational modification in virus surface proteins. These glycans play important roles in the viral life cycle, structure, immune evasion, and cell infection. However, it is necessary to search for new information about viral behavior and immunological host's response after SARS-CoV-2 infection. The present review discusses the implications of the CoV-2 S protein glycosylation in the SARS-CoV-2/ACE2 interaction and the immunological response. Elucidation of the glycan repertoire on the spike protein can propel research for the development of an appropriate vaccine.

Amplificación de ADN isotérmica mediada por horquillas para el diagnóstico de tuberculosis en el contexto mexicano / Loop-mediated isothermal amplification of DNA for the diagnosis of tuberculosis in the Mexican context

Resumen: La tuberculosis es una de las principales causas de mortalidad en todo el mundo asociadas con un agente infeccioso. Aunque se trata de una enfermedad curable, el control de su diseminación es complicado debido a la dificultad en realizar el diagnóstico y al retraso en el inicio del tratamiento. En años recientes se han desarrollado nuevas tecnologías para detectar a los sujetos enfermos, lo que ha resultado en un repertorio amplio de herramientas diagnósticas. Sin embargo, estas tecnologías tienen alto costo y no están disponibles en la mayor parte de los países en desarrollo. En este contexto, la amplificación isotérmica mediada por horquillas ofrece ventajas sobre otras técnicas para el diagnóstico de tuberculosis en áreas con escasos recursos debido a su bajo costo y sencillez metodológica. La evidencia de su eficacia y precisión posicionan a este método como una opción útil en países como México, donde la mayoría de los pacientes acuden a hospitales periféricos con pobre infraestructura.

Abstract: Tuberculosis is a leading cause of morbidity and mortality worldwide associated with a single pathogen. Even when it is a curable disease, the control of its dissemination is complicated due of the difficulty in making the diagnosis and delay in starting treatment. Recently, new technologies to detect infected individuals resulting in a broader repertoire of diagnostic methods have been developed. However, such technologies are expensive and not widely available in most of the developing countries. In this context, loop-mediated isothermal amplification of DNA offers advantages over other tools for the diagnosis of tuberculosis in areas with scarce resources due of its lower cost and methodological feasibility. The current evidence of its efficacy and accuracy place this method as a suitable option applicable in countries like Mexico, where most of the patients attend to regional hospitals and peripheral units with poor infrastructure.

Memory of Natural Killer Cells: A New Chance against Mycobacterium tuberculosis?

Natural killer (NK) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb) has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB), especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called "innate memory," could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb.

Tuberculosis "the great imitator": False healing and subclinical activity.

Tuberculosis is still being a health problem worldwide despite it being a curable disease. Although the only way to prevent its spread is treating cases of active pulmonary disease, we still do not have reliable markers that help us to evaluate the response to anti-tuberculosis drugs. Currently, a patient with negative conversion in the culture of the sputum is considered as cured; however, several studies have questioned the usefulness of this test given that some individuals persist with data of clinical activity despite their negative culture. A couple of recent studies based on sophisticated imaging techniques confirm the above and show us a broader clinical spectrum of the disease, with false healing and subclinical activity in the affected lung tissue even in the absence of symptoms, forcing us to reconsider the way in which we classify tuberculosis and led us to question the efficacy of the current schemes to treat this illness. Here, we comment the findings of these trials and analyze what is their influence in the view of physicians for future applications in diagnosis and/or therapeutics of tuberculosis.