Leprosy Mailing List – May 10, 2026
From: Joel Almeida, Mumbai, India
____________________________________________________________________________
Dear Pieter and colleagues
Macrophages form an important first line of defence. They can limit or even eliminate the bacillus, including via autophagy and vit D-induced cathelicidin. Most of the genomic polymorphisms known to modify the risk of HD, and LL HD, are related to macrophage function (hLife 2024;2:6–17). The well-known importance of nutrition, schooling, income etc is likely to be partly via upholding macrophage function. Infection with the bacilli has been demonstrated in as many as 50% of all individuals in endemic areas [BMJ. 1973; 3:557-559], but new cases of disease are relatively rare in endemic populations, often <1 in 10,000/year. Apparently, most infected persons self-limit or eliminate the bacilli without signs of disease, or sequelae, or onward transmission. They are harmless.
Macrophage function unfortunately can be subverted, by producing bacillary debris (eg., DNA) in the cytosol (J Inf Dis 2016, 214:311-320). Once the bacilli within macrophages are damaged by any means, the resulting molecular cascade of harm (cGAS-STING-IRF3-IFNB-OASL) suppresses autophagy and cathelicidin (J Inf Dis 2016, 214:311-320). The disarmed macrophage is vulnerable to regrowth or reinfection when anti-microbial cover is prematurely withdrawn. The bacillary debris is not cleared immediately, given suppression of autophagy. Therefore the duration of anti-microbial cover is no less important than bactericidal potency. As long as concentrated viable bacilli remain available in the household, or market place, or workplace, or neighbourhood, the disarmed macrophage following the withdrawal of anti-microbial protection forms a hospitable niche for bacilli to replicate.
Bacilli replicate by elongation [Nature Comms (2020) 11:452], boosting the surface area and surface virulence factors per bacillus (Mce1A for invasiveness/cell entry [PLoS Negl Trop Dis 13(3): e0006704] and PGL1 for damage to axonal mitochondria via macrophage iNOS- excess NO [Cell (2017)170, 973–985]). Replicating bacilli have high phenotypic virulence. The predicted outcome of prematurely withdrawn antimicrobials is boosted transmission, more frequent multi-case households, more "silent" nerve damage via PGL1-iNOS-NO. Worse, visible deformity via "silent" nerve damage is predicted to more frequently form the first detectable sign of disease in a subclinically infected contact who was given chemoprophylaxis.
Is it wise to sabotage macrophage defences in asymptomatic contacts?
With all sincerity,
Joel Almeida
____________________________________________________________________________
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << edit...@gmail.com
You received this message because you are subscribed to the Google Groups "Leprosy Mailing List" group.
To unsubscribe from this group and stop receiving emails from it, send an email to leprosymailinglist+unsubscribe@googlegroups.com.
To view this discussion visit https://groups.google.com/d/msgid/leprosymailinglist/96f866fe-6d05-40cc-8bb2-446114d9bdean%40googlegroups.com.
No comments:
Post a Comment