A Serum Factor Mediates Type-2 Immunogen Sensing by Resident Lymph Node Macrophages

Introduction: Schwannomas—Schwann cells–originating tumors—may develop in many locations. However, primary schwannomas arising within lymph nodes are extremely rare, with only a few cases described to this date in the English literature. For the intranodal location, most of the cases are described in the abdominal cavity. In these cases, clinicians may consider and check for familial disorders, such as neurofibromatosis type 2 (NF2) and schwannomatosis also called neurofibromatosis type 3. Schwannomas are benign neoplasms. Histologically, differential diagnosis for spindle-cell lesions in lymph nodes is important and must be done carefully, mainly because they may be attributable to metastatic disease. We report a case of a primary schwannoma arising in a cervical lymph node. Background: Primary schwannomas arising within lymph nodes are extremely rare, with only a few cases reported. Since they are benign neoplasms, the differential diagnosis with other intranodal spindle cell lesions, mostly malignant, is important. Methods: An asymptomatic 69-year-old woman, previously submitted to left hemithyroidectomy for a benign folicular nodule, underwent thyroidectomy totalization following the identification of a large thyroid nodule in routine evaluation. Results: Gross and microscopic examination and ancillary studies were consistent with the diagnosis of intranodal schwannoma. The patient had acquired bilateral hypoacusia. Therefore, type 2 neurofibromatosis was considered and vestibular schwannomas ruled out. Conclusion: Herein, we present the second case of a primary schwannoma in a cervical lymph node reported so far. The relevance of the differential diagnosis is highlighted.

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Comparative Pathogenicity of Nine US Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Isolates in a Five-Week-Old Cesarean-Derived, Colostrum-Deprived Pig Model

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063879600800103 ◽

1996 ◽

Vol 8 (1) ◽

pp. 11-20 ◽

Cited By ~ 156

Author(s):

Patrick G. Halbur ◽

Prem S. Paul ◽

Xiang-Jin Meng ◽

Melissa A. Lum ◽

John J. Andrews ◽

...

Keyword(s):

Lymph Node ◽

Respiratory Disease ◽

Mononuclear Cells ◽

Lung Lesion ◽

Pig Model ◽

Respiratory Syndrome Virus ◽

Lung Lesions ◽

Follicular Hyperplasia ◽

Lung Lobes

One hundred forty-six 5-week-old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated intranasally with 1 of 9 US porcine reproductive and respiratory syndrome virus (PRRSV) isolates. Differences were found in severity of clinical respiratory disease, rectal temperatures ( P ≤0.001), gross lung lesions ( P ≤ 0.001), and microscopic lung lesions ( P ≤ 0.05). Gross lung lesions were generally most severe 10 days postinoculation and were distributed primarily in the cranial, middle, and accessory lobes and ventromedial portion of the caudal lung lobes. Mean gross lung lesion scores estimating the percentage of lung affected by pneumonia at 10 days postinoculation ranged from 16.7% ± 2.8% (x X ± SEM, n = 10) for isolate ISU-51 to 62.4% ± 5.7% ( n = 10) for isolate ISU-28. Microscopic lung lesions were characterized by hyperplastic and hypertrophied type 2 pneumocytes, septal infiltration by mononuclear cells, and accumulation of necrotic alveolar exudate. Lymph node follicular hyperplasia and focal necrosis was seen with all 9 isolates. This CDCD pig model was useful for demonstration of significant differences in pathogenicity among US PRRSV isolates. This difference in pathogenicity may help explain the variation in severity of clinical disease observed in field outbreaks of porcine reproductive and respiratory syndrome and should provide for meaningful comparison of PRRSV genotypes.

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Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis

Journal of Experimental Medicine ◽

10.1084/jem.190.3.385 ◽

1999 ◽

Vol 190 (3) ◽

pp. 385-398 ◽

Cited By ~ 242

Author(s):

Gabriel A. Rabinovich ◽

Gordon Daly ◽

Hanna Dreja ◽

Hitakshi Tailor ◽

Clelia M. Riera ◽

...

Keyword(s):

Lymph Node ◽

T Cell ◽

Interleukin 2 ◽

Disease Onset ◽

Therapeutic Effects ◽

Collagen Induced Arthritis ◽

Gene Therapy Protocol ◽

Lymph Node Cells

Galectin-1 (GAL-1), a member of a family of conserved β-galactoside–binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2–polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1–expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an Aq-restricted, collagen type 2–specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1–mediated autoimmune disorders.

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Apoptosis in lymphoid organs of pigs naturally infected by porcine circovirus type 2

Journal of General Virology ◽

10.1099/vir.0.80221-0 ◽

2004 ◽

Vol 85 (10) ◽

pp. 2837-2844 ◽

Cited By ~ 41

Author(s):

Ana R. Resendes ◽

Natàlia Majó ◽

Joaquim Segalés ◽

Enric Mateu ◽

Maria Calsamiglia ◽

...

Keyword(s):

Lymph Node ◽

Viral Load ◽

B Cell ◽

Inguinal Lymph Node ◽

Porcine Circovirus Type ◽

Porcine Circovirus ◽

Lymphoid Tissues ◽

Lymphoid Depletion ◽

Superficial Inguinal Lymph Node

The objective of the present study was to evaluate the involvement of apoptosis in the development of post-weaning multisystemic wasting syndrome (PMWS) lymphoid-depletion lesions. Twenty-one pigs that were categorized into three different lesional severity stages (S1, n=5; S2, n=7; S3, n=9) and five healthy control pigs (stage S0) were used. From all pigs, samples of thymus, spleen, tonsil, ileum and superficial inguinal lymph node were processed for histological examination, in situ hybridization for porcine circovirus type 2 (PCV2) detection and cleaved caspase-3 (CCasp3) immunohistochemistry for detection of apoptotic cells. PCV2 was quantified in serum samples by using TaqMan real-time PCR. CCasp3 labelling was measured in the different morphological compartments of all lymphoid tissues, using an automated system for quantification. Differences between each tissue compartment and lesional stage were assessed, as well as the correlation between apoptosis, lesional stage and viral load. Overall, the results indicated that the more intense the lymphoid depletion, the lower the rate of apoptosis. In the thymus, the cortex was the area where differences between PMWS-affected and control animals were more evident; it was found that all PMWS-affected pigs had significantly lower rates of apoptosis than the controls. In the secondary lymphoid organs, B-cell areas presented higher rates of apoptosis; similar apoptotic rates were found in this compartment in control and S1 pigs. In S2 and S3, B-cell areas were lost and the apoptotic pattern observed was a diffusely distributed low rate of positive cells. Significantly lower rates of apoptosis between PMWS-affected pigs and the control group were already evident in S1 for the thymus, spleen, superficial inguinal lymph node and Peyer's patches, but not for the tonsils. Apoptotic rates in lymphoid tissues were correlated inversely with viral load in serum and with severity of lesions. In conclusion, the results indicate that apoptosis is not a remarkable feature in PMWS lymphoid lesion development.

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Spatial and temporal regulation of cytokine expression in Type 2 immune responses

10.26686/wgtn.17013620.v1 ◽

2021 ◽

Author(s):

◽

Ryan Kyle

Keyword(s):

T Cells ◽

Lymph Node ◽

Immune Responses ◽

Cd4 T Cells ◽

Helminth Infection ◽

Allergic Inflammation ◽

Nippostrongylus Brasiliensis ◽

Reporter Mice

<p>Type 2 immune responses are generated to provide protection against parasitic helminth infections, however these responses also cause the pathologies associated with allergic inflammation. Studies of the cell types and signalling pathways that mediate Type 2 immune responses have been previously undertaken with the goals of efficient development of vaccines against helminths, and identification of pathways that can be inhibited to decrease the damage caused by allergic inflammation. The cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13) mediate many of the downstream effector functions of the Type 2 immune response. To study the mechanisms that control expression of these two cytokines I have used a novel dual cytokine IL-4 and IL-13 transgenic reporter mouse. Utilising this tool along with other IL-4 reporter mice I have discovered that the amount of T cell receptor (TCR) signalling modulates the allelic expression of IL-4 by CD4⁺ T cells. The transgenic IL-4 reporter mouse has for the first time allowed independent measurement of the effects of IL-4 deficiency on the expression of IL-4 in vivo. Using this system I have found that IL- 4 is not required for the in vivo generation or expansion of IL-4 producing CD4⁺ T cells. Th2 differentiated CD4⁺ T cells also expresses IL-13, however the dual reporter mice have demonstrated that IL-13 is expressed consistently later than IL-4 in vitro, and IL-13 requires constant, or multiple exposures to TCR stimulus for expression to be induced. IL-13 expression is absent from lymph node CD4⁺ T cells during exposure to allergens or helminth infection. Sequestration of CD4⁺ T cells in the lymph node does not impact the number of IL-13 expressing CD4⁺ T cells in the lung during a helminth infection, indicating that adaptive immune cell derived IL-13 may be entirely produced by lung resident cells not requiring transit through the lymph node. I have characterised a population of innate lymphoid cells (ILCs) within the skin and found that the proportion of these cells that constitutively express IL-13 decreases with age. These cells did not drastically change in numbers or IL-13 responses in a range of inflammatory conditions including a model of atopic dermatitis. Basophils were found to respond to the atopic dermatitis model by migrating specifically to the treated skin site and draining lymph node, and producing IL-4 in a thymic stromal lymphopoietin dependant manner. Treatment with exogenous cytokines induced IL-13 expression from group 2 ILCs (ILC2s) in the lung and these cells promoted protective immune responses against Nippostrongylus brasiliensis infection. The immune response generated during a primary infection by Nippostrongylus brasiliensis provides protection from re-infection. Long-term protection is dependent on CD4⁺ T cells but when sufficiently stimulated by cytokine, ILC2s can rescue the protection lost by the depletion of CD4⁺ T cells. This thesis has shown that CD4⁺ T cells and populations of innate immune cells differentially regulate the expression of the closely related Type 2 cytokines IL-4 and IL- 13. These discoveries will help direct future research aiming to boost the effectiveness of anti-helminth vaccines, or decrease the pathology caused by allergic diseases by targeting specific cytokine expression.</p>

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Prior Exposure to Ortho-Phthalaldehyde Augments IgE-Mediated Immune Responses to Didecyldimethylammonium Chloride: Potential for 2 Commonly Used Antimicrobials to Synergistically Enhance Allergic Disease

Toxicological Sciences ◽

10.1093/toxsci/kfaa112 ◽

2020 ◽

Vol 178 (1) ◽

pp. 127-137

Author(s):

Hillary L Shane ◽

Ewa Lukomska ◽

Lisa Weatherly ◽

Rachel Baur ◽

Stacey E Anderson

Keyword(s):

Lymph Node ◽

T Cell ◽

B Cells ◽

Immune Responses ◽

Allergic Disease ◽

Cell Activation ◽

Immunological Mechanisms ◽

Draining Lymph Node ◽

Ige Mediated

Abstract Health-care workers have an increased incidence of allergic disease compared with the general public and are exposed to a variety of high-level disinfectants. Although exposure to these agents has been associated with allergic disease, findings between epidemiology and animal studies often conflict respecting immunological mechanisms. Therefore, we hypothesized that previous exposure to a representative IgE-mediated sensitizer (ortho-phthalaldehyde [OPA]) alters immune responses to a representative T-cell-mediated sensitizer (didecyldimethlyammonium chloride [DDAC]). Here, BALB/c mice were topically exposed to OPA (0.5%) for 3 days, rested, then topically exposed to DDAC (0.0625%, 0.125%, and 0.25%) for 14 days. Coexposure resulted in phenotypic changes in draining lymph node (dLN) cells, including a decreased frequency of CD8+ T cells and increased frequency and number of B cells compared with DDAC-only treated mice. The coexposed mice also had enhanced Th2 responses, including significant alterations in: dLN Il4 (increased), B-cell activation (increased), CD8+ T-cell activation (decreased), and local and systemic IgE production (increased). These changes were not observed if mice were exposed to DDAC prior to OPA. Exposure to OPA alone shows Th2 skewing, indicated by increased activation of skin type 2 innate lymphoid cells, increased frequency and activation of draining lymph node B cells, and increased levels of type 2 cytokines. These findings suggest that the OPA-induced immune environment may alter the response to DDAC, resulting in increased IgE-mediated immune responses. This data may partially explain the discordance between epidemiological and laboratory studies regarding disinfectants and provide insight into the potential immunological implications of mixed chemical exposures.

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Deficiency of Lymph Node-Resident Dendritic Cells (DCs) and Dysregulation of DC Chemoattractants in a Malnourished Mouse Model of Leishmania donovani Infection

Infection and Immunity ◽

10.1128/iai.01778-14 ◽

2014 ◽

Vol 82 (8) ◽

pp. 3098-3112 ◽

Cited By ~ 10

Author(s):

Marwa K. Ibrahim ◽

Jeffrey L. Barnes ◽

E. Yaneth Osorio ◽

Gregory M. Anstead ◽

Fabio Jimenez ◽

...

Keyword(s):

Dendritic Cells ◽

Lymph Node ◽

Lymph Nodes ◽

Leishmania Donovani ◽

Significant Risk ◽

Significant Risk Factor ◽

Content Type ◽

Susceptibility To Infection ◽

Increased Susceptibility

ABSTRACTMalnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoanLeishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination ofL. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes ofL. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination ofL. donovaniis related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways.

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Inflammation rapidly recruits mammalian GMP and MDP from bone marrow into regional lymphatics

eLife ◽

10.7554/elife.66190 ◽

2021 ◽

Vol 10 ◽

Author(s):

Juana Serrano-Lopez ◽

Shailaja Hegde ◽

Sachin Kumar ◽

Josefina Serrano ◽

Jing Fang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Lymph Node ◽

Systemic Inflammation ◽

Myeloid Cell ◽

Innate Immune ◽

Lymphatic Circulation ◽

Myeloid Progenitor ◽

Mechanistic Basis

Innate immune cellular effectors are actively consumed during systemic inflammation but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NFkB independent, Traf6/IkB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+ conventional dendritic cells type 2 (cDC2) and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node (LN) myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation.

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Development of Sarcocystis in mule deer transmitted through dogs and coyotes

Canadian Journal of Zoology ◽

10.1139/z83-378 ◽

1983 ◽

Vol 61 (12) ◽

pp. 2904-2912 ◽

Cited By ~ 7

Author(s):

J. P. Dubey ◽

T. P. Kistner ◽

Gayle Callis

Keyword(s):

Lymph Node ◽

Mule Deer ◽

Odocoileus Hemionus ◽

Additional Information ◽

Mesenteric Lymph ◽

Hepatic Lymph Node ◽

Muscular Tissues ◽

Sarcocyst Wall

Tissues from 13 experimentally inoculated mule deer (Odocoileus hemionus) from Oregon, studied by G. Hudkins and T. P. Kistner in 1976 and L. D. Koller, T. P. Kistner, and G. Hudkins in 1977, were reexamined. The following additional information on Sarcocystis hemionilatrantis was obtained. Two types of meronts were found in deer necropsied between 29 and 41 days postinoculation (DPI). Type 1 meronts were in capillaries in adrenal glands, kidney, lymph node, lung, choroid plexi, and spleen; meronts were 20.5 × 13.5 μm (14−32 × 10−20 μm; n = 26) and contained 20 to 35 nuclei. Type 2 meronts were found in macrophages in muscular tissues; these meronts were 20 × 14 μm (10−35 × 7−19 μm; n = 7) and contained 10 to 60 merozoites. Sarcocysts were seen in three deer at 63, 65, and 90 DPI. At 63 and 65 DPI sarcocysts were immature and their walls were thin (< 1 μm) and smooth. At 90 DPI, sarcocysts were up to 525 μm long and 50 μm wide; the sarcocyst wall was 1 to 2 μm thick and cross striated. In the same deer another type of mature sarcocyst was also seen; sarcocysts were up to 825 μm long, the walls were 2 to 4 μm thick and lacked cross striations. Two additional 3-day-old deer were inoculated orally with sporocysts from the feces of a dog fed meat from a mule deer from Montana naturally infected with Sarcocystis sp. Deer No. 1, fed 107 sporocysts, was killed at 14 DPI and deer No. 2, fed 5 × 106 sporocysts, was killed at 24 DPI. At 14 DPI, meronts were found in capillaries and arteries in the lung, heart, and spleen; the meronts were 26.5 × 20 μm (14−39 × 14−25 μm; n = 31) and contained up to 100 nuclei. At 24 DPI, intravascular meronts were found in the spinal cord, hepatic lymph node, kidney, thyroid gland, and mesenteric lymph node. In addition, meronts were found in macrophages in muscular tissues; these meronts were 16 × 10 μm (10−28 × 7−14 μm; n = 10) and contained up to 40 nuclei.

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