scholarly journals Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 9436-9440 ◽  
Author(s):  
Gregg A. Dean ◽  
Niels C. Pedersen

ABSTRACT Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-γ). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-γ, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-γ, IL-12p40 and IL-10. An increase in IFN-γ, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4+ cells were the primary source of IL-2, IL-4, and IL-10. Both CD4+ and CD8+ cells produced IFN-γ, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.

2001 ◽  
Vol 82 (9) ◽  
pp. 2225-2234 ◽  
Author(s):  
Carmen Cantó-Nogués ◽  
Sue Jones ◽  
Rebecca Sangster ◽  
Peter Silvera ◽  
Robin Hull ◽  
...  

The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID50 of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer (P<0·05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.


1985 ◽  
Vol 161 (3) ◽  
pp. 475-489 ◽  
Author(s):  
S H Lee ◽  
P M Starkey ◽  
S Gordon

We have estimated the macrophage content of different tissues of the normal adult mouse using F4/80, a highly specific antigen marker for mature mouse macrophages. An absorption indirect binding assay was used to quantitate F4/80 antigen against a calibration standard made from the J774.2 macrophage-like cell line. The richest sources of tissue F4/80 antigen were found to be bone marrow, spleen, cervical and mesenteric lymph nodes, large bowel, liver, kidneys, and small bowel. The organs that have the highest total F4/80 antigen content are the liver, large bowel, small bowel, bone marrow, spleen, cervical and mesenteric lymph nodes, and kidney. We conclude that the mononuclear phagocyte system is mainly distributed in the gastrointestinal tract and liver, followed by hemopoietic and lymphoid tissues.


2014 ◽  
Vol 82 (9) ◽  
pp. 3704-3712 ◽  
Author(s):  
Maria M. Figueiredo ◽  
Beatriz Deoti ◽  
Izabela F. Amorim ◽  
Aldair J. W. Pinto ◽  
Andrea Moraes ◽  
...  

ABSTRACTUsing flow cytometry, we evaluated the frequencies of CD4+and CD8+T cells and Foxp3+regulatory T cells (Tregs) in mononuclear cells in the jejunum, colon, and cervical and mesenteric lymph nodes of dogs naturally infected withLeishmania infantumand in uninfected controls. All infected dogs showed chronic lymphadenitis and enteritis. Despite persistent parasite loads, no erosion or ulcers were evident in the epithelial mucosa. The colon harbored more parasites than the jejunum. Frequencies of total CD4+, total Foxp3, and CD4+Foxp3+cells were higher in the jejunum than in the colon. Despite negative enzyme-linked immunosorbent assay (ELISA) serum results for cytokines, levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α) were higher in the jejunum than in the colon for infected dogs. However, IL-4 levels were higher in the colon than in the jejunum for infected dogs. There was no observed correlation between clinical signs and histopathological changes or immunological and parasitological findings in the gastrointestinal tract (GIT) of canines with visceral leishmaniasis. However, distinct segments of the GIT presented different immunological and parasitological responses. The jejunum showed a lower parasite load, with increased frequencies and expression of CD4, Foxp3, and CD8 receptors and IL-10, TGF-β, IFN-γ, and TNF-α cytokines. The colon showed a higher parasite load, with increasing expression of IL-4.Leishmania infantuminfection increased expression of CD4, Foxp3, IL-10, TGF-β, IFN-γ, and TNF-α and reduced CD8 and IL-4 expression in both the jejunum and the colon.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3896-3896
Author(s):  
Calvin M. Johnson ◽  
Ayalew Mergia ◽  
Janelle Novak ◽  
Nazareth Gengozian

Abstract Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naïve CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T− lymphocytes; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the CD45RA+ subpopulation. In FIV infected cats, the fate of naïve CD4 lymphocytes is unknown due to the lack of specific markers. Recently, a mAb (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of naïve CD4 and CD8 lymphocytes in cats. The purpose of this study was to characterize the fate of CD4+CD45RA+ blood cells eight weeks after FIV infection. One-day-old kittens (n=6) were infected with virions either from a wild type clone (JSY3) or mutant ORF-A clone at equivalent reverse transcriptase units and compared to historical control data. Eight weeks after inoculation, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. Both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 13% in controls to 8% in infected cats (P=0.004), contributing to a reduction in the CD4:CD8 ratio from 2.45 in controls to 0.76 in infected cats (P=0.007). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 69% of CD4+ cells were CD45RA+ in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naïve CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8+ cells were CD45RA+ in FIV infected cats as compared to 80% in controls). The distribution of CD45RA+ cells in the lymph nodes of FIV infected cats mirrored those in the blood. Together, these data suggest that acute FIV infection results in a rapid depletion of naïve CD4 lymphocytes throughout the blood and secondary lymphoid tissues, while proportions of naïve CD8 lymphocytes remain unchanged. CD4+CD45RA+ cells may be depleted during pediatric FIV infection through lytic infection or a transition to a memory phenotype lacking CD45RA.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249341
Author(s):  
Fang Xu ◽  
Lili Tian ◽  
Yan Li ◽  
Xuelian Zhang ◽  
Yayin Qi ◽  
...  

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) represents one of major zoonotic diseases among cattle, it also affects the health of human, other domestic animals and wild life populations. Inhalation of infected aerosol droplets is considered as the most frequent route of the infection. This study aims to investigate the current forms of tuberculosis in cattle and identify the possible transmission modes in dairy farms of China. 13,345 cows from eight dairy farms in three provinces were comprehensively diagnosed by a multitude of assays, including SIT, CIT, IFN-γ assay and ELISA. It has been indicated that advanced infection of bTB was found in 752 (5.64%) cattle, suggesting a high prevalence of tuberculosis in these dairy farms. In the necropsy examination of 151 positive cattle, typical bTB lesions were observed in 131 cattle (86.75%), of which, notably, 90.84% lesions appeared in liver, spleen, mesenteric lymph nodes, mammary lymph nodes and other organs, taking up a large proportion among cattle with advanced bTB infection. 71.26% extrapulmonary tuberculosis (EPTB) was related to gastrointestinal system. M. bovis nucleic acid was further found in milk and feces samples and M. bovis was even isolated from milk samples. Phylogenetic analysis based on whole genome sequencing unraveled that six isolates were closely related to M. bovis AF2122/97 originated from UK, whereas four isolates shared close relation to M. bovis 30 from China, respectively. Our data demonstrate that the increase of EPTB transmitted by digestive tract is implicated in the current high prevalence rate of bTB in China, which also provides leads for bTB control in other countries with high prevalence of bTB in the future.


2014 ◽  
Vol 63 (12) ◽  
pp. 1741-1749 ◽  
Author(s):  
Ivanna S. Rolny ◽  
Jessica Minnaard ◽  
Silvia M. Racedo ◽  
Pablo F. Pérez

Bacillus cereus is a spore-forming micro-organism responsible for foodborne illness. In this study, we focus on the host response following intragastric challenge with a pathogenic B. cereus strain (B10502) isolated from a foodborne outbreak. C57BL/6J female mice were infected by gavage with strain B10502. Controls were administered with PBS. Infection leads to significant modification in relevant immune cells in the spleen, Peyer's patches (PP) and mesenteric lymph nodes (MLN). These findings correlated with an increase in the size of PP as compared with uninfected controls. Histological studies showed that B. cereus infection increased the ratio of intestinal goblet cells and induces mononuclear cell infiltrates in spleen at 5 days post-infection. Evaluation of cytokine mRNA expression demonstrated a significant increase in IFN-γ in MLN after 2 days of infection. The present work demonstrates that infection of mice with vegetative B. cereus is self-limited. Our findings determined relevant cell populations that were involved in the control of the pathogen through modification of the ratio and/or activation.


1995 ◽  
Vol 6 (4) ◽  
pp. 230-238 ◽  
Author(s):  
K. K. Manouilov ◽  
I. I. Fedorov ◽  
F. D. Boudinot ◽  
C. A. White ◽  
L. P. Kotra ◽  
...  

Human immunodeficiency virus appears to be proliferating within the lymphatic system throughout the period of clinical latency. Targeting of anti-HIV compounds to the lymphatic tissue may therefore provide therapeutic benefits. The purpose of this investigation was to determine the distribution of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZdU) in lymph nodes in a mouse model after administration of the lipophilic prodrugs dipalmitoylphosphatidyl-azidodeoxythymidine (DPP-AZT) and dipalmitoylphosphatidyl-azidodideoxyuridine (DPP-AZdU). Mice received 50 mg kg−1 of parent nucleoside and 164 mg kg−1 of DPP-AZT (equivalent to 50 mg kg−1 AZT) intravenously or orally and 180mg kg−1 DPP-AZdU (equivalent to 50 mg kg−1 AZdU) orally. Serum, neck, axillary and mesenteric lymph nodes were collected at selected times and AZT and AZdU concentrations were determined by HPLC. The disposition of AZT and AZdU in serum and lymph nodes was significantly altered after intravenous and oral administration of DPP-AZT and oral administration of DPP-AZdU when compared to that after administration of parent nucleoside. Lower peak concentrations of AZT and AZdU were observed in serum and lymph nodes after administration of the phospholipid prodrugs. However, DPP-AZT and DPP-AZdU produced consistently higher concentrations of AZT and AZdU, respectively, 2-3 h after prodrug administration. Half-life values for both nucleosides in serum and lymph nodes were significantly greater after prodrug administration. Greater AUC values for nucleosides were noted in neck (AZT and AZdU) and mesenteric (AZT) lymph nodes after administration of prodrugs compared with values obtained for parent drugs. Furthermore, relative lymph node exposure to AZT and AZdU in the lymph nodes was greater after administration of prodrug than after administration of parent compound. Thus, DPP-AZT and DPP-AZdU show potential as useful prodrugs for the delivery of AZT and AZdU to the lymphatic system.


2019 ◽  
Vol 56 (5) ◽  
pp. 681-690 ◽  
Author(s):  
Natividad Bellido-Carreras ◽  
Héctor Argüello ◽  
Sara Zaldívar-López ◽  
Ángeles Jiménez-Marín ◽  
Rodrigo P. Martins ◽  
...  

Salmonella is a major foodborne pathogen and pork is one of the main sources of human salmonellosis. Understanding the pathogenesis and progression of the infection within the host is of interest to establish potential approaches to control the disease in pigs. The present study evaluates factors such as intestinal colonization, fecal shedding, and pathogen persistence by 2 studies using experimental challenge with Salmonella Typhimurium in weaned pigs and euthanasia at different time points (1, 2, and 6 and 2, 14, and 30 days postinfection [dpi], respectively). Histopathology of intestine at early time points (1 dpi and 2 dpi) showed severe damage to the epithelium together with an increase in polymorphonuclear cells and macrophages ( P < .001), particularly in jejunum and ileum. Large quantities of Salmonella were detected within the contents of the ileum, cecum, and colon in early infection. Salmonella could also be observed in the medulla of tonsils and mesenteric lymph nodes. From 6 dpi onward, signs of recovery were observed, with progressive restoration of the epithelium, reduction of the inflammatory infiltrate, and elimination of Salmonella from the mucosa. Concentration of Salmonella in feces and ileum content decreased, but shedding did not cease even at 4 weeks after infection. Persistence of the bacteria in mesenteric lymph nodes was identified within the connective tissue at 14 and 30 dpi. Our results demonstrate a recovery of the disease after an initial acute phase but also show persistence within the lumen and surrounding lymphoid tissue. These findings are relevant to developing effective control strategies.


2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Emma C. Mackley ◽  
Stephanie Houston ◽  
Clare L. Marriott ◽  
Emily E. Halford ◽  
Beth Lucas ◽  
...  

Abstract Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control of CD4 T-cell responses to commensal bacteria. It is not known whether ILC populations migrate from their mucosal and peripheral sites to local draining secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the interfollicular areas of mucosal draining lymph nodes, forming a distinct microenvironment not observed in peripheral lymph nodes. By photoconverting intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from the intestine to the draining mesenteric lymph nodes, which specifically for the LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining lymph nodes using different mechanisms.


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