Kinome Analysis of Cattle Peripheral Lymph Nodes to Elucidate Differential Response to Salmonella spp.

Salmonella spp., contained within the peripheral lymph nodes (PLNs) of cattle, represents a significant source of contamination of ground beef. Herein is the first report where species-specific kinome peptide arrays designed for bovine biology were used to further the understanding of Salmonella spp. within these PLNs. For the purpose of this research, multiple comparisons of sub-iliac lymph nodes were made to include nodes from feedlot cattle that were infected with Salmonella spp. to those that were non-infected; seasonal differences in feedlot cattle harvested in either August or January; cull dairy cows compared to feedlot cattle; and PLNs from cattle experimentally inoculated with Salmonella spp. versus naturally infected animals. The first comparison of Salmonella-positive and -negative PLNs found that considering the kinotypes for these animals, the major distinguishing difference was not the presence or absence of Salmonella spp. in the PLNs but the concentration. Further, the majority of pathways activated were directly related to immune responses including innate immunity, thus Salmonella spp. within the PLNs activates the immune system in that node. Results from the comparison of feedlot cattle and cull dairy cows suggests that a Salmonella spp.-negative animal, regardless of type, has a more consistent kinome profile than that of a Salmonella spp.-positive animal and that the differences between feedlot and cull dairy cattle are only pronounced when the PLNs are Salmonella spp. positive. PLNs collected in the winter showed a much more consistent kinome profile, regardless of Salmonella status, suggesting that in the winter these cattle are similar, and this is not affected by the presence of Salmonella spp., whereas significant variability among kinotypes was observed for PLNs collected in the summer. The most distinct clustering of kinotypes observed in this study was related to how the animal was infected with Salmonella spp. There were significant differences in the phosphorylation state of the immune response peptides between experimentally and naturally infected animals, suggesting that the immune system is activated in a significantly different manner when comparing these routes of infection. Increasing our understanding of Salmonella spp. within cattle, and specifically within the PLNs, will ultimately help design effective pre-harvest intervention strategies as well as appropriate experimentation to validate those technologies.

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Lymphadenopathy

10.1093/med/9780199568741.003.0036 ◽

2018 ◽

Author(s):

Chris Bunch

Keyword(s):

Immune System ◽

Lymph Nodes ◽

The Body ◽

Peripheral Lymph ◽

Small Bean

Lymph nodes are small, bean-shaped structures generally a few millimetres in size, distributed widely throughout the body and assuming a major role in the immune system. Peripheral lymph nodes are not normally palpable except in thin individuals. Enlargement of lymph nodes is called lymphadenopathy. It is important to distinguish between reactive lymphadenopathy, which is usually an appropriate response to infection or inflammation, and malignant or neoplastic lymphadenopathy.

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HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+T Lymphocytes

Journal of Virology ◽

10.1128/jvi.00611-15 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5687-5700 ◽

Cited By ~ 24

Author(s):

Lia Vassena ◽

Erica Giuliani ◽

Herwig Koppensteiner ◽

Sebastian Bolduan ◽

Michael Schindler ◽

...

Keyword(s):

T Cells ◽

Plasma Membrane ◽

T Lymphocytes ◽

Cell Surface ◽

Immune Responses ◽

Lymph Nodes ◽

Viral Proteins ◽

Peripheral Lymph ◽

Leukocyte Homing ◽

Hiv 1

ABSTRACTLeukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses.IMPORTANCEL-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis.

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Investigation into Possible Differences in Salmonella Prevalence in the Peripheral Lymph Nodes of Cattle Derived from Distinct Production Systems and of Different Breed Types†

Journal of Food Protection ◽

10.4315/0362-028x.jfp-15-198 ◽

2015 ◽

Vol 78 (11) ◽

pp. 2081-2084 ◽

Cited By ~ 10

Author(s):

T. R. BROWN ◽

T. S. EDRINGTON ◽

G. H. LONERAGAN ◽

D. L. HANSON ◽

K. MALIN ◽

...

Keyword(s):

Beef Cattle ◽

Lymph Nodes ◽

Production Systems ◽

Feedlot Cattle ◽

Intervention Strategies ◽

Beef Steers ◽

Cull Cows ◽

Peripheral Lymph ◽

Brahman Cattle ◽

Collection Period

Previous research demonstrated significant variation in the prevalence of Salmonella in peripheral lymph nodes (LNs) of feedlot cattle and cull cows, with greater prevalence in feedlot cattle. Therefore, we performed experiments to investigate whether these differences in Salmonella prevalence in subiliac LNs are due to, or influenced by, breed, which in many respects is a proxy for the production system in which the animal is derived. Holstein steers are a by-product of dairy systems, and beef steers are an intended product of commercial beef operations. For the first experiment, Holstein and beef steers originating from the same feedlot and harvested on the same day were sampled. Of the 467 Holstein and 462 beef cattle LNs collected, 62.1% of Holstein and 59.7% of beef cattle samples harbored Salmonella (P = 0.46; qualitative culture), with 51.2 and 48.9% of samples containing quantifiable concentrations (P = 0.49), respectively. The concentration of Salmonella within the LN followed a decreasing trend over the collection period (May to October), averaging 1.4 log CFU/g of LN for both Holstein and beef cattle samples (P = 0.78). In a second experiment, we compared 100% Brahman cattle to their beef cattle counterparts, as we hypothesized that the resistance of Brahman cattle to insects may reduce Salmonella transmission via biting insects. Of the 42 Brahman and 31 beef cattle LNs collected, the concentration of Salmonella within the LN averaged 3.0 log CFU/g for Brahman cattle and 2.9 log CFU/g for beef cattle samples (P = 0.30). Using qualitative culture, we recovered Salmonella from 100% of LNs from Brahman cattle and 97% of beef cattle samples (P = 0.25). Results of this research indicate that the differences observed are not due to breed and are likely a function of age, immune function, or other factors yet to be identified. Understanding which cattle are more likely to harbor Salmonella within LNs will aid in targeting both pre- and postharvest intervention strategies.

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The atypical chemokine receptor CCX-CKR scavenges homeostatic chemokines in circulation and tissues and suppresses Th17 responses

Blood ◽

10.1182/blood-2010-01-264390 ◽

2010 ◽

Vol 116 (20) ◽

pp. 4130-4140 ◽

Cited By ~ 56

Author(s):

Iain Comerford ◽

Robert J. B. Nibbs ◽

Wendel Litchfield ◽

Mark Bunting ◽

Yuka Harata-Lee ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Lymph Nodes ◽

Chemokine Receptor ◽

Fold Increase ◽

Wild Type ◽

Peripheral Lymph ◽

The Central Nervous System

Abstract Our previous in vitro studies led to proposals that the atypical chemokine receptor CCX-CKR is a scavenger of CCR7 ligand homeostatic chemokines. In the present study, we generated CCX-CKR−/− mice and confirm this scavenger function in vivo. Compared with wild-type mice, CCX-CKR−/− have a 5-fold increase in the level of CCL21 protein in blood, and 2- to 3-fold increases in CCL19 and CCL21 in peripheral lymph nodes. The effect of these protein increases on immunity was investigated after immunization with MOG35-55 peptide emulsified in complete Freund adjuvant (CFA). The subsequent characteristic paralysis develops with enhanced kinetics and severity in CCX-CKR−/− versus wild-type mice. Despite this effect, antigen-specific immune responses in the draining lymph nodes are diminished in CCX-CKR−/− mice. Instead, the earlier onset of disease is associated with enhanced T-cell priming in the CCX-CKR−/− spleen and a skewing of CD4+ T-cell responses toward Th17 rather than Th1. This observation correlates with increased expression of IL-23 in the CCX-CKR−/− spleen and increased CCL21 levels in the central nervous system postimmunization. The early onset of disease in CCX-CKR−/− mice is reversed by systemic administration of neutralizing anti-CCL21 antibodies. Thus, by regulating homeostatic chemokine bioavailability, CCX-CKR influences the localization, kinetics, and nature of adaptive immune responses in vivo.

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Aging-Related Cellular, Structural and Functional Changes in the Lymph Nodes: A Significant Component of Immunosenescence? An Overview

Cells ◽

10.3390/cells10113148 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3148

Author(s):

Marta Cakala-Jakimowicz ◽

Paulina Kolodziej-Wojnar ◽

Monika Puzianowska-Kuznicka

Keyword(s):

Immune System ◽

Immune Responses ◽

Lymph Nodes ◽

Immune Cell ◽

Humoral Response ◽

The Elderly ◽

Cell Types ◽

Functional Changes ◽

B Cell Homeostasis

Aging affects all tissues and organs. Aging of the immune system results in the severe disruption of its functions, leading to an increased susceptibility to infections, an increase in autoimmune disorders and cancer incidence, and a decreased response to vaccines. Lymph nodes are precisely organized structures of the peripheral lymphoid organs and are the key sites coordinating innate and long-term adaptive immune responses to external antigens and vaccines. They are also involved in immune tolerance. The aging of lymph nodes results in decreased cell transport to and within the nodes, a disturbance in the structure and organization of nodal zones, incorrect location of individual immune cell types and impaired intercellular interactions, as well as changes in the production of adequate amounts of chemokines and cytokines necessary for immune cell proliferation, survival and function, impaired naïve T- and B-cell homeostasis, and a diminished long-term humoral response. Understanding the causes of these stromal and lymphoid microenvironment changes in the lymph nodes that cause the aging-related dysfunction of the immune system can help to improve long-term immune responses and the effectiveness of vaccines in the elderly.

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Characterization of local and peripheral immune system in pregnant and non-pregnant ewes

Journal of Animal Science ◽

10.1093/jas/skab208 ◽

2021 ◽

Author(s):

Laurel D Quirke ◽

Paul H Maclean ◽

Neville A Haack ◽

Sara J Edwards ◽

Axel Heiser ◽

...

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Immune System ◽

T Cell ◽

Lymph Nodes ◽

Early Pregnancy ◽

Reproductive Tract ◽

Reproductive Tissue ◽

Expression Of Genes ◽

Peripheral Lymph

Abstract Modulation of the immune system is known to be important for successful pregnancy but how immune function might differ between the lymph nodes draining the reproductive tract and peripheral lymph nodes is not well understood. Additionally, if immune system changes in response to the presence of an embryo during early pregnancy, and if this response differs in local versus peripheral immune tissue, has not been well characterized. To address these questions, we examined expression of genes important for immune function using NanoString technology in the ampulla and isthmus of the oviduct, endometrium, lymph nodes draining the reproductive tract (lumbo-aortic and medial iliac) as well as a peripheral lymph node (axillary), the spleen and circulating immune cells from ewes on day 5 of the estrous cycle or pregnancy. Concentrations of estradiol and progesterone in plasma were also determined. Principal component analysis revealed separation of the local from the peripheral lymph nodes (MANOVA P = 3.245e-08, R 2 = 0.3) as well as separation of tissues from pregnant and non-pregnant animals [lymph nodes (MANOVA P = 2.337e-09, R 2 = 0.5), reproductive tissues (MANOVA P = 2.417e-14, R 2 = 0.47)]. Nine genes were differentially (FDR <0.10) expressed between lymph node types, with clear difference in expression of these genes between the lumbo-aortic and axillary lymph nodes. Expression of these genes in the medial iliac lymph node was not consistently different to either the axillary or the lumbo-aortic lymph node. Expression of IL10RB was increased (P < 0.05) by 24% in the reproductive tissue of the pregnant animals comparing to non-pregnant animals. Analysis of gene categories revealed that expression of genes of the T cell receptor pathway in reproductive tract tissues was associated (P < 0.05) with pregnancy status. In conclusion, assessment of gene expression of reproductive and immune tissue provides evidence for a specialization of the local immune system around the reproductive tract potentially important for successful establishment of pregnancy. Additionally, differences in gene expression patterns in reproductive tissue from pregnant and non-pregnant animals could be discerned as early as day 5 of pregnancy. This was found to be associated with expression of genes important for T-cell function and thus highlights the important role of these cells in early pregnancy.

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