Activation of host nucleic acid sensors by Mycobacterium: good for us or good for them?

Although the importance of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sensors in controlling viral infection is well established, their role in promoting an effective immune response to pathogens other than viruses is less clear. This is particularly true for infections with mycobacteria, as studies point to both protective and detrimental roles for activation of nucleic acid sensors in controlling a mycobacterial infection. Some of the contradiction likely stems from the use of different model systems and different mycobacterial species/strains as well as from which nucleic acid sensors were studied and what downstream effectors were evaluated. In this review, we will describe the different nucleic acid sensors that have been studied in the context of mycobacterial infections, and how the different studies compare. We conclude with a section on how nucleic acid sensor agonists have been used therapeutically and what further information is needed to enhance their potential as therapeutic agents.

Viral and immunologic evaluation of smokers with severe COVID-19.

Smoking negatively affects B cell function and immunoglobulin levels, but it is unclear if this immune dysfunction contributes to the risk of severe COVID-19 in smokers. We evaluated binding IgM, IgA and IgG antibodies to spike and receptor binding domain antigens, and used a pseudovirus assay to quantify neutralization titers in a set of 27 patients with severe COVID-19. We found no significant differences between binding and neutralization antibody responses for people with a smoking history and people who never smoked. High plasma viral load, but not antibody titers, was linked to an increased risk of death. Humoral immune dysfunction was not a major driver of severe COVID-19 in smokers.