The role of gut microbiota in eye diseases / 中华实验眼科杂志

In recent years, the study of symbiotic microbial community on human health and disease has gradually become a hot spot.In particular, the Human Microbiome Project and the emergence of 16S rRNA gene sequencing technology have further promoted the study of human-related microbiota.The gut microbiota is the largest microecosystem of the human body.Normal gut microbiota plays an important role in maintaining host immune balance, promoting nutrient metabolism and sustaining intestinal homeostasis.At present, there is increasing evidence that gut microbiota disorders are associated with a variety of diseases, not only having an impact on the intestinal tract but also affecting many extraintestinal tissues and organs.With the emergence of the concept of gut-brain axis, which interacts between gut microbiota and brain, some researchers suggest that there may also be gut-eye axis between gut microbiota and eye.This review summarized the recent research advances on the role of gut microbiota in ophthalmic diseases, including corneal diseases, uveitis, retinopathies, and the ophthalmic diseases associated with systemic diseases, in the hope that it could provide evidence for the existence of gut-eye axis and new idea for the treatment of ophthalmic diseases in the future.

Mechanism of action of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in liver diseases / 临床肝胆病杂志

Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.

Mechanism of autophagy in the development and progression of autoimmune hepatitis / 临床肝胆病杂志

Autophagy is a process of self-defense and self-repair of cells and tissues and plays an important role in regulating the body's immune inflammatory response and maintaining the homeostasis of liver cells. This article summarizes the mechanism of autophagy in the development and progression of autoimmune hepatitis (AIH) from the aspects of the role of autophagy in regulating immune inflammatory response, regulating immune signal transduction, and preventing overactivated innate immune response. It is believed that autophagy may reveal the mechanism of AIH and provide new ideas and methods for the research on AIH.

Hepatitis B cured by the activation of intrahepatic innate immunity: Research advances and new strategies / 临床肝胆病杂志

Host innate and adaptive immune responses are essential for the clearance of hepatitis B virus (HBV). Patients with chronic HBV infection have defects in innate and specific immune responses against HBV, which cannot effectively eliminate the virus and may result in persistent virus replication and liver inflammation. In addition to direct inhibition of HBV, treatment strategies targeting host immunity, such as stimulating or restoring antiviral immunity, are also important methods to achieve functional cure in patients with chronic hepatitis B. The liver is the target organ for HBV infection, and therefore, the research on the impact of HBV infection on intrahepatic immune microenvironment has become a hotspot for the research and development of new drugs that regulate the antiviral immune response against HBV in the liver. This article reviews the recent research advances in innate immune response associated with HBV infection and the new strategies to activate intrahepatic innate immune response and achieve the cure of hepatitis B.

Inmunología de la leptospirosis / Immunology of leptospirosis

Resumen Leptospirosis es una enfermedad re-emergente de distribución mundial ocasionada por espiroquetas patogénicas del género Leptospira que afectan humanos, animales domésticos o silvestres. Las manifestaciones clínicas de la enfermedad son diversas y son el resultado de la interacción de la respuesta inmune del hospedador y las condiciones de virulencia propias de las especies patógenas. Aunque se desconocen muchos aspectos de la inmunidad en la infección por Leptospira spp, es reconocido que los hospe deros susceptibles presentan diferencias en su respuesta inmune, como la activación/evasión del sistema del complemento, la activación de sub poblaciones celulares, la producción de citoquina y el desarrollo de anti cuerpos. El estudio del perfil inmunológico en pacientes con leptospirosis ha sido documentado y contribuye en la identificación de biomarcadores asociados con severidad. Esta revisión presenta algunos de los eventos relacionados con la respuesta inmune desde el ingreso de la bacteria en la fase inicial de la infección hasta su multiplicación y generación de enfer medad en el humano.

Abstract Leptospirosis is a re-emergent disease of worldwide distribution caused by pathogenic spirochetes of the Leptospira genus that affect humans, do mestic and wild animals. The clinical manifestations of the disease are diverse and are the result of the interaction of the immune response of the host and the virulence conditions of the pathogenic species. Although many aspects of immunity in infection with Leptospira spp are unknown, it is recognized that susceptible hosts show differences in their immune res ponse, such as activation / evasion of the complement system, activation of cellular subpopulations, production of cytokines, development of anti bodies. Study of the immunological profile in patients with leptospirosis has been documented and contributes in the identification of bio-markers associated with severity. This review presents updated events related to the immune response from the entry of the bacteria in the initial phase of the infection to its multiplication and generation of human disease.

Pathogenesis of vitiligo / 中华皮肤科杂志

While researches about pathogenesis of vitiligo have focused on intrinsic abnormalities of melanocytes and T cell-mediated specific immune response targeting melanocytes, the key role of innate immune response induced by intrinsic damage to melanocytes, and that of keratinocytes in the immune microenvironment in vitiligo skin lesions have become new hot spots recently. Many questions still remain unanswered, including how melanocytes trigger innate immune response and activate adaptive immune response, how keratinocytes and T cells alternately regulate skin immune responses, etc. In the next years, understanding how the above factors synergistically contribute to the damage to melanocytes in vitiligo will facilitate further development of new therapies and targeted drugs.

Effect of isotretinoin on peptidoglycan-induced expression of inflammatory genes in human SZ95 sebocytes / 中华皮肤科杂志

Objective To evaluate the effect of isotretinoin on expression of ache-associated inflammatory genes induced by peptidoglycan in human SZ95 sebocytes,and to explore the molecular mechanism underlying the treatment of acne with isotretinoin.Methods Cultured SZ95 sebocytes were divided into 3 groups:control group receiving no treatment,peptidoglycan group treated with 20 mg/L peptidoglycan alone,and costimulation group treated with 20 mg/L peptidoglycan combined with 10-5 mol/L isotretinoin.After 3-hour treatment,real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of pro-inflammatory cytokines including interleukin (IL)-1α,IL-1β,IL-6,IL-8,tumor necrosis factor (TNF)-α,Toll-like receptor 2 (TLR2) and MyD88 (a downstream gene of TLR2) in SZ95 sebocytes in the above groups.After 24-hour treatment,enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of IL-1α,IL-1β,IL-6,IL-8 and TNF-α in the cell culture supernatant in the above groups.After 48-hour treatment,Western blot analysis was conducted to determine the protein expression of TLR2 and MyD88.Statistical analysis was carried out with SPSS 23 software by one-way analysis of variance (ANOVA) for the comparison among the 3 groups,and by Bonferroni method for multiple comparisons.Results The mRNA and protein expression of pro-inflammatory cytokines including IL-1α,IL-1β,IL-6,IL-8 and TNF-α all significantly differed among the 3 groups (all P ＜ 0.01),and was significantly higher in the peptidoglycan group than in the control group and costimulation group (both P ＜ 0.016 7).The mRNA expression of MyD88 also significantly differed among the control group,peptidoglycan group and costimulation group (6.707 ± 0.950,10.270 ± 0.477,7.892 ± 0.900 respectively,F =10.17,P ＜ 0.01),and was significantly higher in the peptidoglycan group than in the control group and costimulation group (t =4.740,3.298 respectively,both P ＜ 0.016 7).The mRNA and protein expression of TLR2 were markedly higher in the peptidoglycan group than in the control group,but did not differ between the peptidoglycan group and the costimulation group.Conclusion Isotretinoin can inhibit peptidoglycan-induced expression of inflammatory factors possibly associated with the occurrence of acne in human SZ95 sebocytes,likely by inhibiting the expression of MyD88,but not TLR2,in the innate immune response,which may be one of the mechanisms underlying the treatment of acne with isotretinoin.

Pathogenesis of vitiligo / 中华皮肤科杂志

While researches about pathogenesis of vitiligo have focused on intrinsic abnormalities of melanocytes and T cell-mediated specific immune response targeting melanocytes,the key role of innate immune response induced by intrinsic damage to melanocytes,and that of keratinocytes in the immune microenvironment in vitiligo skin lesions have become new hot spots recently.Many questions still remain unanswered,including how melanocytes trigger innate immune response and activate adaptive immune response,how keratinocytes and T cells alternately regulate skin immune responses,etc.In the next years,understanding how the above factors synergistically contribute to the damage to melanocytes in vitiligo will facilitate further development of new therapies and targeted drugs.

Nueva teoría sobre la depresión: un equilibrio del ánimo entre el sistema nervioso y el inmunológico, con regulación de la serotonina-quinurenina y el eje hipotálamo-hipófiso-suprarrenal / A new theory of depression based on the serotonin/kynurenine relationship and the hypothalamic-pituitary-adrenal axis

La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema inmunológico, propone que ciertos tipos de estrés distorsionan la relación entre la actividad del sistema inmunitario innato y la del sistema nervioso central. El estrés causado por una infección o el estrés psicológico excesivo activan receptores de tipo toll, como el TLR-4, el factor de transcripción NF-kB, el inflamasoma NLRP3, así como la secreción de interleucina 1 beta (IL-1ß) e interleucina 6 (IL-6); esto causa, en primer lugar, los síntomas generales de enfermedad que aparecen con cualquier infección, pero también los síntomas característicos de la depresión como disforia y anhedonia. Las evidencias indican que, si el estímulo persiste o se repite en las siguientes 24 horas, se activa la enzima indolamina 2,3-dioxigenasa (IDO) de la vía metabólica de la quinurenina, lo cual incrementa la síntesis del ácido quinolínico y reduce la síntesis de serotonina. El ácido quinolínico activa los receptores de N-metil-D-aspartato (NMDA) en el sistema nervioso central y estimula la secreción de, entre otras, las interleucinas IL-6 e 1L-1ß, las cuales promueven la hiperactividad del eje hipotálamohipófiso-suprarrenal y refuerzan la desviación del metabolismo del triptófano hacia la producción de ácido quinolínico, así como de las interleucinas de la inmunidad innata, con lo cual se reduce más la síntesis de serotonina y se consolida el proceso depresivo. Este proceso puede ser iniciado por las interleucinas estimuladas por una infección, así como por algunas vacunas o por un estrés psicológico excesivo que active el eje hipotálamo-hipófiso-suprarrenal simultáneamente con la respuesta inmunológica innata, con lo que se provocaría un proceso de inflamación estéril en el sistema nervioso central.

The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1ß, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.

Immunotherapy may improve functional cure of chronic hepatitis B / 中华临床感染病杂志

Currently, clinical antiviral therapies for chronic hepatitis B virus (HBV) infection can efficiently control HBV replication.However, it remains difficult to achieve HBsAg clearance and sustains off-therapy, that is the functional cure of chronic hepatitis B ( CHB) in most of patients.Host immune responses play critical roles in HBV clearance and HBV infection control by activating innate and adaptive immune responses, resulting in improving the functional cure rate of patients with CHB.This article reviews the recent advances in immunology studies related to functional cure of CHB.

Haplotypes in CCR5-CCR2 , CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort / Los haplotipos en CCR5-CCR2 , CCL3 y CCL5 se asocian con resistencia natural a la infección por el HIV-1 en una cohorte colombiana

RESUMEN Introduction: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. Objective: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Materials and methods: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value <0.05 after Bonferroni correction was considered significant. Results: Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p'<0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Conclusion: Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

ABSTRACT Introducción. Algunas variantes en genes que codifican los correceptores del HIV-1 y sus ligandos se han asociado individualmente a la resistencia natural frente a dicha infección. Sin embargo, su presencia simultánea ha sido poco estudiada. Objetivo. Evaluar la asociación de haplotipos individuales y multilocus en genes que codifican los correceptores virales CCR5 y CCR2 y sus ligandos CCL3 y CCL5 con la resistencia o la propensión a la infección por el HIV-1. Materiales y métodos. Nueve variantes en CCR5-CCR2, dos en CCL3 y dos en CCL5 fueron genotipificadas mediante reacción en cadena de la polimerasa de polimorfismos de longitud de fragmentos de restricción (Restriction Fragment Length Polymorphism-PCR-RFLP) en 35 individuos seropositivos (casos) y 49 seronegativos expuestos (controles) de Colombia. Los haplotipos se infirieron utilizando el programa Arlequín, y su frecuencia individual o combinada se comparó en los casos y los controles mediante la prueba de ji al cuadrado. Se consideró significativo un valor de p'<0,05 después de la corrección de Bonferroni. Resultados. La homocigosis del haplogrupo humano (HH) E estaba ausente en los controles y era frecuente en los casos, es decir, con tendencia hacia la propensión. Los haplotipos C-C y T-T en CCL3 se asociaron con la propensión (p'=0,016) y la resistencia (p'<0,0001), respectivamente. Por último, en el análisis multilocus, el haplotipo combinado formado por HHC en CCR5-CCR2, T-T en CCL3 y G-C en CCL5 se asoció con la resistencia (p'=0,006). Conclusión. Los resultados de este estudio sugieren que ciertas combinaciones específicas de variantes en los genes de una misma vía de señalización pueden definir un fenotipo resistente al HIV-1. Aunque el tamaño de la muestra era pequeño, las asociaciones estadísticamente significativas sugieren un efecto considerable; sin embargo, estos resultados deben validarse en cohortes de mayor tamaño.

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands

Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. METHODS: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. RESULTS: This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). CONCLUSIONS: TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR.

Inflammasomes and dermatology

Abstract: 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.

Skin barrier in atopic dermatitis: beyond filaggrin

Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Influence of hepatitis B virus infection on intrahepatic natural killer cells and innate lymphoid cell 22 / 临床肝胆病杂志

ObjectiveTo investigate the influence of hepatitis B virus (HBV) infection on intrahepatic natural killer (NK) cells and innate lymphoid cell 22 (ILC22), and to provide theoretical and experimental bases for clarifying mechanisms of HBV infection in inducing innate immune response. MethodsA total of 10 male BALC/c aged 6-8 weeks were divided into experimental group and control group, with 5 mice in each group. The mice in the experimental group were treated with the hydrodynamic injection of normal saline containing 10 μg plasmids of complete HBV genome (the volume equaled to 9% of the body weight of the mouse) via the caudal vein, and those in the control group were only treated with normal saline. The mice were scarified 4 days later, and intrahepatic lymphocytes (IHLs) were isolated. Flow cytometry was used to determine the proportions of NK cells and ILC22 subset in IHLs, and the t-test was used for comparison between groups. ResultsHydrodynamic injection of the plasmids containing complete HBV genome induced high levels of HBsAg and HBeAg in mice, with an increase in the serum level of alanine aminotransferase. After HBV infection, the experimental group showed a significant increase in the proportion of intrahepatic NK cells compared with the control group (25.90%±4.92% vs 12.98%±2.13%, t=3.811, P=0.003), while there were no significant differences in the proportions of CD127+ and CD127- NK subsets in NK cells between the two groups. Moreover, after HBV infection, the experimental group showed a significant increase in the proportion of intrahepatic NKp46+ILC22 subset compared with the control group (36.05%±6.85% vs 10.22%±3.54%, t=7.372, P＜0001); however, there was no significant difference in the proportion of NKp46-ILC22 between the two groups. ConclusionHBV infection induces increased levels of intrahepatic NK cells and NKp46+ILC22 cells and thus promotes the innate immune response in the liver.

Lower Levels of Urinary Nerve Growth Factor Might Predict Recurrent Urinary Tract Infections in Women / 대한배뇨장애요실금학회지

PURPOSE: To investigate the changes in urinary nerve growth factor (uNGF) levels after acute urinary tract infection (UTI) and to assess the role of uNGF in predicting UTI recurrence in women. METHODS: Women with uncomplicated, symptomatic UTIs were enrolled. Cephalexin 500 mg (every 6 hours) was administered for 7-14 days to treat acute UTIs. Subsequently, the patients were randomized to receive either sulfamethoxazole/trimethoprim 800 mg/160 mg daily at bedtime, or celecoxib 200 mg daily for 3 months and were monitored for up to 12 months. NGF levels in the urine were determined at baseline, 1, 4, and 12 weeks after the initiation of prophylactic therapy, and were compared between women with first-time UTIs and recurrent UTIs, sulfamethoxazole/trimethoprim and celecoxib-treated women, and no UTI recurrence and UTI recurrence that occurred during the follow-up period. Twenty women free of UTIs served as controls. RESULTS: A total of 139 women with UTI and 20 controls were enrolled in the study, which included 50 women with a first-time UTI and 89 women with recurrent UTIs. Thirty-seven women completed the study. Women with recurrent UTIs (n=23) had a trend of lower uNGF levels than women with first-time UTIs (n=14). During follow-up, 9 women had UTI recurrence. The serial uNGF levels in women with UTI recurrence were significantly lower than those in women who did not have UTI recurrence during the follow-up period. CONCLUSIONS: The lower levels of uNGF in women with recurrent UTI and the incidence of UTI recurrence during follow-up suggest that lower uNGF might reflect the defective innate immunity in women with recurrent UTI.

Small Heterodimer Partner and Innate Immune Regulation

The nuclear receptor superfamily consists of the steroid and non-steroid hormone receptors and the orphan nuclear receptors. Small heterodimer partner (SHP) is an orphan family nuclear receptor that plays an essential role in the regulation of glucose and cholesterol metabolism. Recent studies reported a previously unidentified role for SHP in the regulation of innate immunity and inflammation. The innate immune system has a critical function in the initial response against a variety of microbial and danger signals. Activation of the innate immune response results in the induction of inflammatory cytokines and chemokines to promote anti-microbial effects. An excessive or uncontrolled inflammatory response is potentially harmful to the host, and can cause tissue damage or pathological threat. Therefore, the innate immune response should be tightly regulated to enhance host defense while preventing unwanted immune pathologic responses. In this review, we discuss recent studies showing that SHP is involved in the negative regulation of toll-like receptor-induced and NLRP3 (NACHT, LRR and PYD domains-containing protein 3)-mediated inflammatory responses in innate immune cells. Understanding the function of SHP in innate immune cells will allow us to prevent or modulate acute and chronic inflammation processes in cases where dysregulated innate immune activation results in damage to normal tissues.

O sistema imunológico do recém-nascido / The newborn?s immune system

Os recém-nascidos e lactentes jovens apresentam seu sistema imunológico imaturo, oque os torna mais suscetíveis aos agentes infecciosos presentes nesse período. Sabe-seque os neonatos são mais vulneráveis às infecções que as crianças e os adultos. Diferençasobservadas na imunidade inata e adaptativa são responsáveis pelo prejuízo dasdefesas do neonato. Os defeitos da imunidade adaptativa requerem o contato préviocom antígenos, enquanto o sistema inato não necessita de experiência imunológicaprévia. A imunidade inata é a primeira linha de defesa contra os patógenos e é compostapela resposta de granulócitos, monócitos, macrófagos, células dendríticas e naturalkiller. Alguns patógenos responsáveis pelas infecções intraútero, intraparto e pós-partoestimulam a resposta imune fetal e neonatal. Esse agentes incluem o estreptococodo grupo B, a Escherichia coli, a Listeria monocytogenes, o herpes simples, o citomegalovírus,o vírus Epstein-Barr, o vírus varicella-zoster, o vírus respiratório sincicial, oToxoplasma gondii e a Candida albicans. O melhor entendimento do funcionamento dosistema imunológico no período neonatal é capaz de tornar o médico apto a desempenharmedidas preventivas e terapêuticas que melhorem os cuidados das infecçõesdurante esse período. Essa revisão tem como objetivo discutir avanços recentes e o entendimentoatual da imunidade do recém-nascido, dando ênfase aos aspectos imunológicosrelacionados à acentuada susceptibilidade às infecções, as quais são responsáveispor significante morbimortalidade no período neonatal.

Newborns and young infants present an immature immune system, which makes them more susceptible to infectious agents present during this period. It is known that newborns are more vulnerable to infections than children and adults. Observed differences in the innate and adaptive immunity are responsible for decreased neonate?s defenses. The defects in the adaptive immunity require previous contact with antigens, while theinnate system requires no prior immune experience. The innate immunity is the first line of defense against pathogens and is composed by the responses from granulocytes, monocytes, macrophages, and dendritic and natural killer cells. Some pathogens, responsible for intra-uterus, intra-partum, and postpartum infections stimulate fetal and neonatal immune responses. These agents include the group B streptococcus, Escherichiacoli, Listeria monocytogenes, herpes simplex virus, Cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, respiratory syncytial virus, Toxoplasma gondii, and Candida albicans. A better understanding of the functioning of the immune system in the neonatal period allows the doctor to perform preventive and therapeutic measures that improve the care of infections during this period. This review aims to discuss recent advances and current understanding on the newborn?s immunity focusing on immunological aspects related to their enhanced susceptibility to infections, which are responsible for significant morbidity and mortality in the neonatal period.

Role of inflammasome activation in development and exacerbation of asthma

Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.