Infectious neuropathies

Sindic, Christian

doi:10.1097/wco.0b013e328364c036

Cited by 27 publications

(16 citation statements)

References 29 publications

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“…The occurrence of polyneuropathy due to various infectious agents is well recognized in the literature [ 16 ]. Among them, nerve damage in leprosy leading to permanent disability still represents an important global health problem.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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 in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1404-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Except for the disease duration, no additional parameter has been found to be associated to the onset of PN, including viral load or genotype, severity of liver disease, and cryocrit level . The involvement of small nerve fibres is clinically characterized by painful, burning feet , but pure motor polyneuropathy as well as autonomic or demyelinating neuropathies can less frequently occur .…”

Section: Introductionmentioning

confidence: 99%

HCV RNA Genomic sequences and HCV‐E2 glycoprotein in sural nerve biopsies from HCV‐infected patients with peripheral neuropathy

Russi

Sansonno

Monaco

et al. 2017

Neuropathology Appl Neurobio

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“…Enhanced pain sensitivity is a hallmark of inflammation and is a debilitating feature of many clinical diseases, including chronic Human Immunodeficiency Virus-1 (HIV-1) infections [ 1 , 2 ]. However the underlying causes of chronic pain remain poorly defined [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase

Huang

Souza

et al. 2016

PLoS Pathog

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Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO). Here we show that acute influenza A virus (IAV) and chronic murine leukemia retrovirus (MuLV) infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS) tissues. Moreover, kynurenine (Kyn), a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19) and dendritic cell (CD11c) markers (CD19+ DCs). CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg) DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC) phenotypes, unlike conventional (CD19neg) DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19+ DCs expressing IDO in host responses to MuLV infection that enhance pain hypersensitivity and cause immune pathology. Collectively, our findings support the hypothesis elevated IDO activity in non-CNS due to virus infections causes pain hypersensitivity mediated by Kyn. Previously unappreciated links between host immune responses to virus infections and pain sensitivity suggest that IDO inhibitors may alleviate heightened pain sensitivity during infections.

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Infectious neuropathies

Abstract: Recent data have improved our knowledge and diagnostic tools of infectious neuropathies. Treatment of the injured nerves is not yet available, and prevention and rapid diagnosis remain the main priorities for the clinician.

Cited by 27 publications

References 29 publications

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

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

HCV RNA Genomic sequences and HCV‐E2 glycoprotein in sural nerve biopsies from HCV‐infected patients with peripheral neuropathy

Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase

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