Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.

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“…The synthesis of IL-1β in vitro in macrophages derived from monocytes, through the NLRP3 inflammasome pathway, was also observed. 122 …”

Section: Dermatological Diseases Associated With Inflammasomesmentioning

confidence: 99%

Inflammasomes and dermatology

Sá

Neto

2016

An. Bras. Dermatol.

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“…This inflammatory pathway also applies to other STIs; for example, the LPS of N. gonorrhoeae has been shown to harbour hexa‐acylated lipid A, which can activate the NRLP3 inflammasome . H. ducreyi elicits IL‐1β responses that are dependent on activation of caspase‐1, ‐5 and NLRP3 in both M1 and 2 macrophages . In viral STIs such as HPV, cytosolic viral DNA is detected by AIM2 inflammasome and IFI16, an intracellular DNA sensor, resulting in the production of IL‐1β and IFN‐β respectively.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

et al. 2019

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Introduction Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non‐immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk. Discussion STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub‐mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue‐resident cells that may also display innate‐like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert. Conclusions STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under‐appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub‐clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection.

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“…Haemophilus ducreyi infection activates the inflammasome in monocyte-derived macrophages and experimentally infected human skin (48). Secretion of NLRP3-dependent IL-1β in macrophages is dependent on both caspase-1 and caspase-5.…”

Section: Chlamydia Infectionmentioning

confidence: 99%

“…However, these results have been observed with caspase-1 and caspase-5 inhibitors, and further studies using genetic knockdown tools are required to substantiate this data. Interestingly, this activation is limited to M1 and M2 macrophages while non-polarized macrophages fail to activate inflammasomes, suggesting that the precise contribution of inflammasomes in human lesions cannot be directly extrapolated (48) (Table 1; Figure 1). …”

Section: Chlamydia Infectionmentioning

confidence: 99%

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

et al. 2016

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Inflammasomes are multiprotein complexes present in the cytosol as pattern recognition receptors or as sensors of damage-associated molecular patterns. After recognition of microbe-associated molecular patterns or host-derived danger signals, nucleotide oligomerization domain-like receptors oligomerize to form inflammasomes. The activation of inflammasomes results in an alarm, which is raised to alert adjacent cells through the processing and release of a number of other substrates present in the cytosol. A wide array of inflammasomes and their adapter molecules have been identified in the host’s innate immune system in response to various pathogens. Components of specific pathogens activate different inflammasomes, which once activated in response to pathogen-induced infection, induce the activation of caspases, and the release of mature forms of interleukin-1β (IL-1β) and IL-18. Identifying the mechanisms underlying pathogen-induced inflammasome activation is important if we are to develop novel therapeutic strategies to target sexually transmitted infections (STIs) related pathogens. This information is currently lacking in literature. In this review, we have discussed the role of various inflammasomes in sensing different STIs, as well as the beneficial or detrimental effects of inflammasome signaling in host resistance. Additionally, we have discussed both canonical and non-canonical processing of IL-1β induced with respect to particular infections. Overall, these findings transform our understanding of both the basic biology and clinical relevance of inflammasomes.

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Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Cited by 5 publications

References 79 publications

Inflammasomes and dermatology

Inflammasomes and dermatology

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

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