Friendly pathogens: prevent or provoke autoimmunity

Sathyabama, Sathyaseelan; Khan, Nargis; Agrewala, Javed N.

doi:10.3109/1040841x.2013.787043

Cited by 13 publications

(7 citation statements)

References 80 publications

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“…Thereby, when microbial dysbiosis occurs, CNS dysfunction could result from the autoimmune reaction caused by molecular mimicry between bacteria and hostself proteins, as in case of multiple sclerosis. 121 Multiple sclerosis, a devastating autoimmune disease that leads to progressive deterioration of neurologic function, has been shown to be profoundly influenced by the gut microbiota via its ability to stimulate proinflammatory T-cell responses during experimental-associated encephalomyelitis. 45 Moreover, the commensal microbes were shown to be essential in triggering immune processes that led to a relapsing-remitting autoimmune disease driven by myelin-specific CD4 þ T cells.…”

Section: When Intimate Friends Turn Into Foesmentioning

confidence: 99%

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Aidy

Dinan

Cryan

2015

Clinical Therapeutics

170

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Section: When Intimate Friends Turn Into Foesmentioning

confidence: 99%

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Aidy

Dinan

Cryan

2015

Clinical Therapeutics

170

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“…In this way, the gut microbes can modulate, tune and tame the host immune response [72]. Dysbiosis of the microbial community can lead to the development of autoimmunity [72,73], and experimental findings indicate that both autoimmune encephalomyelitis [74] and autoimmune demyelination [75] involve the gut microbiota. There is also evidence that the formation of autoantibodies against neuropeptides is governed by intestinal microbes [76][77][78].…”

Section: Neuropeptide Autoantibodies Under the Control Of The Intestimentioning

confidence: 99%

Neuropeptides and the Microbiota-Gut-Brain Axis

Holzer

Farzi

2014

Advances in Experimental Medicine and Biology

349

267

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Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gutbrain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gutbrain axis address 4 information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and 4 information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G proteincoupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiotagut-brain axis in health and disease.

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“…As Damian first pointed out, parasites evade immune surveillance by mimicking host antigens (Damian, 1965;Damian, 1967;Damian, 1989). Many commensal organisms express antigens that mimic host antigens (e.g., Coyne, et al, 2004;Szymula, et al, 2014) so that tolerance to the microbiome must be balanced with host protection against potentially pathogenic microbes (Stowell, et al, 2014;Sathyabama, et al 2014). I suggest that the degree to which microbial components of the microbiome are tolerated by the host is, in fact, directly related to the degree to which they express host-like antigens (Root- Bernstein, 2016;Root-Bernstein, 2017).…”

Section: Act Provides a Mechanism For Understanding Microbiome Roles mentioning

confidence: 99%

<strong>A General Theory of Autoimmune Disease Causation: Integrating Innate and Adaptive Immunity, Altered Antigen Processing, Sex and Genetic Predispositions, and Microbiome Effects</strong>

Root‐Bernstein¹

2019

Preprint

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Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target.  Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection.  Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

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Friendly pathogens: prevent or provoke autoimmunity

Cited by 13 publications

References 80 publications

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

Neuropeptides and the Microbiota-Gut-Brain Axis

<strong>A General Theory of Autoimmune Disease Causation: Integrating Innate and Adaptive Immunity, Altered Antigen Processing, Sex and Genetic Predispositions, and Microbiome Effects</strong>

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