M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator

Acta Neuropathologica
Nawal Bahia El IdrissiValeria Ramaglia

Abstract

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage ...Continue Reading

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Citations

Sep 22, 2015·Expert Review of Clinical Immunology·Bryan Paul Morgan
Feb 19, 2016·Journal of Neuropathology and Experimental Neurology·Priscila Ribeiro AndradeEuzenir Nunes Sarno
Apr 9, 2016·Journal of Neuroinflammation·Nawal Bahia El IdrissiDirk Troost
Jun 4, 2016·Plastic and Reconstructive Surgery. Global Open·Eric L WanA Lee Dellon
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Mar 23, 2018·PLoS Neglected Tropical Diseases·Débora Santos da SilvaFlavio Alves Lara
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Aug 14, 2020·Ciência & saúde coletiva·Carlos Dornels Freire de SouzaCarlos Feitosa Luna
May 16, 2019·Anais Brasileiros De Dermatologia·Carlos Dornels Freire de SouzaMônica de Avelar Figueiredo Mafra Magalhães
Apr 5, 2019·Journal of the European Academy of Dermatology and Venereology : JEADV·W Alemu Belachew, B Naafs
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Mar 13, 2021·Immunological Reviews·Anouk van Hooij, Annemieke Geluk

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Methods Mentioned

BETA
biopsies
Enzyme-linked immunosorbent assay
ELISA
dissection
biopsy
these

Software Mentioned

Image Pro Plus
LightCycler
Cell D

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