scholarly journals An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control of Cryptosporidium parvum Infection in Mice

2005 ◽  
Vol 73 (12) ◽  
pp. 8425-8428 ◽  
Author(s):  
Brett A. Leav ◽  
Masaru Yoshida ◽  
Kathleen Rogers ◽  
Seth Cohen ◽  
Nihal Godiwala ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Gamma Interferon ◽  
Susceptibility To Infection ◽  
Ifn Γ ◽  
Rapid Kinetics ◽  
And Control ◽  
Kinetics Of

ABSTRACT Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-γ) dependent. Using an IFN-γ-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-γ and demonstrate that CD8+ T-cell receptor αβ intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-γ expression and secretion by naive CD8+ T cells in response to a protozoan pathogen have not previously been demonstrated.

scholarly journals Interleukin-15 May Be Responsible for Early Activation of Intestinal Intraepithelial Lymphocytes after Oral Infection with Listeria monocytogenes in Rats

1998 ◽  
Vol 66 (12) ◽  
pp. 5677-5683 ◽  
Author(s):  
Kenji Hirose ◽  
Hirohiko Suzuki ◽  
Hitoshi Nishimura ◽  
Akio Mitani ◽  
Junji Washizu ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Oral Infection ◽  
Epithelial Cell Line ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Interleukin 15 ◽  
Ifn Γ

ABSTRACT Exogenous interleukin-15 (IL-15) stimulates intestinal intraepithelial lymphocytes (i-IEL) from mice to proliferate and produce gamma interferon (IFN-γ) in vitro. To determine whether endogenous IL-15 is involved in activation of i-IEL during intestinal infection, we examined IL-15 synthesis by intestinal epithelial cells (i-EC) after infection with Listeria monocytogenes in rats. In in vitro experiments, invasion of L. monocytogenes into IEC-6 cells, a rat small intestine epithelial cell line, evidently induced IL-15 mRNA expression coincident with nuclear factor κB (NF-κB) activation, which is essential for IL-15 gene expression. IL-15 synthesis was detected in rat i-EC on day 1 after an oral inoculation of L. monocytogenes in vivo. The numbers of T-cell receptor (TCR) γδ+ T cells, NKR.P1+cells, and CD3+ CD8+ αα cells in i-IEL were significantly increased on day 1 after oral infection. The i-IEL from infected rats produced larger amounts of IFN-γ upon stimulation with immobilized anti-TCR γδ or anti-NKR.P1 monoclonal antibodies. These results suggest that IL-15 produced by i-EC may stimulate significant fractions of i-IEL to produce IFN-γ at an early phase of oral infection with L. monocytogenes.

scholarly journals Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis

2000 ◽  
Vol 68 (9) ◽  
pp. 5393-5400 ◽  
Author(s):  
S. G. Rhodes ◽  
N. Palmer ◽  
S. P. Graham ◽  
A. E. Bianco ◽  
R. G. Hewinson ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Early Increase ◽  
Onchocerca Ochengi ◽  
Ifn Γ ◽  
Bovine Tuberculin ◽  
Kinetics Of ◽  
Experimental Challenge

ABSTRACT This study shows that gamma interferon (IFN-γ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-γ and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-γ was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-γ responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-γ and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of theM. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

scholarly journals Early Induction of Gamma Interferon and Interleukin-10 Production in Draining Lymph Nodes from Mice Infected withBorrelia burgdorferi

2000 ◽  
Vol 68 (12) ◽  
pp. 7162-7165 ◽  
Author(s):  
Frederic Ganapamo ◽  
Vida A. Dennis ◽  
Mario T. Philipp
Keyword(s):  
Differential Susceptibility ◽  
Neutralizing Antibody ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Lyme Arthritis ◽  
Ifn Γ ◽  
Culture Supernatants ◽  
Draining Lymph Nodes ◽  
Cells Cultured

ABSTRACT Lymph node (LN) cells from C3H/HeJ mice (Lyme disease susceptible) infected for 1 week with Borrelia burgdorferi strain JD1 produced higher levels of gamma interferon (IFN-γ) when stimulated in vitro with B. burgdorferi spirochetes than equivalent cells from B. burgdorferi-infected C57BL/6J mice (disease resistant). The interleukin-10 (IL-10) levels were comparable in the two strains, whereas the IL-4 levels were below detection limits.B. burgdorferi-stimulated LN cells from C57BL/6J mice produced significantly higher levels of IFN-γ in the presence of neutralizing anti-IL-10 antibody than cells cultured with B. burgdorferi alone. No effect of IL-10 neutralization on IFN-γ production by LN cells from C3H/HeJ mice was observed. Neutralizing antibody to IFN-γ had no effect on the production of IL-10 by LN cells from C57BL/6J mice. A slight decrease in IL-10 production was detected in culture supernatants of equivalent cells from C3H/HeJ mice. The differential effect of IL-10 on IFN-γ production in C57BL/6J and C3H/HeJ mice suggests that IL-10 is probably involved in the regulation of IFN-γ production by LN cells during infection and may be at the root of the differential susceptibility to Lyme arthritis in these two strains of mice.

scholarly journals Eimeria tenella Infection Induces Local Gamma Interferon Production and Intestinal Lymphocyte Subpopulation Changes

2000 ◽  
Vol 68 (3) ◽  
pp. 1282-1288 ◽  
Author(s):  
Cheol H. Yun ◽  
Hyun S. Lillehoj ◽  
Kang D. Choi
Keyword(s):  
Mrna Expression ◽  
Primary Infection ◽  
Secondary Infection ◽  
Intraepithelial Lymphocytes ◽  
Lymphocyte Subpopulation ◽  
Eimeria Tenella ◽  
Gamma Interferon ◽  
Cecal Tonsil ◽  
Ifn Γ ◽  
Intestinal Lymphocyte

ABSTRACT The role of intestinal lymphocytes and gamma interferon (IFN-γ) production in protective immunity to Eimeria tenellainfection was evaluated in two inbred strains of chickens (SC and TK) that display different patterns of susceptibility to coccidiosis. Oral inoculation of either strain with E. tenella led to parasite invasion of the intestinal cecum and cecal tonsils. Greater fecal oocyst shedding was seen in TK chickens. Flow cytometric analyses of cecal tonsil lymphocytes demonstrated greater numbers of CD4+ and T-cell receptor γδ-positive (TCR1+) cells in SC chickens and elevated numbers of CD8+ and TCR2+ cells in TK chickens following primary infection. IFN-γ mRNA expression was significantly increased in cecal tonsil and intraepithelial lymphocytes at days 6 and 8, respectively, after primary infection in SC compared to TK chickens. While no differences were noted between cecal tonsil lymphocytes of the two strains following secondary infection, TK chickens showed elevated IFN-γ transcript levels in intestinal intraepithelial lymphocytes at this time. Selective depletion of CD4+, but not CD8+, cecal tonsil lymphocytes in SC chickens resulted in a reduced IFN-γ mRNA expression, indicating that CD4+ cells are the primary source of this cytokine. Collectively, these results indicate that local lymphocyte responses and production of IFN-γ are influenced by host genetic factors.

scholarly journals Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity to Cryptosporidium parvum Infection

2009 ◽  
Vol 77 (11) ◽  
pp. 5044-5049 ◽  
Author(s):  
Farah M. Barakat ◽  
Vincent McDonald ◽  
James P. Di Santo ◽  
Daniel S. Korbel
Keyword(s):  
Innate Immunity ◽  
Nk Cells ◽  
Cryptosporidium Parvum ◽  
Neutralizing Antibodies ◽  
Nk Cell ◽  
Protective Role ◽  
Gamma Interferon ◽  
Intestinal Cell ◽  
Chronic Infections ◽  
Ifn Γ

ABSTRACT A gamma interferon (IFN-γ)-dependent innate immune response operates against the intestinal parasite Cryptosporidium parvum in T- and B-cell-deficient SCID mice. Although NK cells are a major source of IFN-γ in innate immunity, their protective role against C. parvum has been unclear. The role of NK cells in innate immunity was investigated using Rag2−/− mice, which lack T and B cells, and Rag2−/− γc −/− mice, which, in addition, lack NK cells. Adult mice of both knockout lines developed progressive chronic infections; however, on most days the level of oocyst excretion was higher in Rag2−/− γc −/− mice and these animals developed morbidity and died, whereas within the same period the Rag2−/− mice appeared healthy. Neonatal mice of both mouse lines survived a rapid onset of infection that reached a higher intensity in Rag2−/− γc −/− mice. Significantly, similar levels of intestinal IFN-γ mRNA were expressed in Rag2−/− and Rag2−/− γc −/− mice. Also, infections in each mouse line were exacerbated by treatment with anti-IFN-γ neutralizing antibodies. These results support a protective role for NK cells and IFN-γ in innate immunity against C. parvum. In addition, the study implies that an intestinal cell type other than NK cells may be an important source of IFN-γ during infection and that NK cells may have an IFN-γ-independent protective role.

scholarly journals The Early Kinetics of Cytomegalovirus-Specific CD8+ T-Cell Responses Are Not Affected by Antigen Load or the Absence of Perforin or Gamma Interferon

2008 ◽  
Vol 82 (10) ◽  
pp. 4931-4937 ◽  
Author(s):  
Daniel M. Andrews ◽  
Christopher E. Andoniou ◽  
Peter Fleming ◽  
Mark J. Smyth ◽  
Mariapia A. Degli-Esposti
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
T Cell Responses ◽  
Gamma Interferon ◽  
Murine Cytomegalovirus ◽  
Cell Responses ◽  
Ifn Γ ◽  
T Cell Expansion ◽  
Kinetics Of

ABSTRACT Both innate and adaptive immune responses participate in the control of murine cytomegalovirus (mCMV) infection. In some mouse strains, like BALB/c, the control of infection relies on the activities of CD8+ T cells. mCMV-specific CD8+ T-cell responses are unusual in that, even after mCMV has been controlled in the periphery, the numbers of circulating virus-specific CD8+ T cells remain high compared to those observed in other viral infections. To better understand the generation and maintenance of mCMV-specific CD8+ T-cell responses, we evaluated how antigen load and effector molecules, such as perforin (Prf) and gamma interferon (IFN-γ), influence these responses during acute infection in vivo. Viral burden affected the magnitude, but not the early kinetics, of antigen-specific CD8+ T-cell responses. Similarly, the magnitude of virus-specific CD8+ T-cell expansion was affected by Prf and IFN-γ, but contraction of antigen-specific responses occurred normally in both Prf- and IFN-γ-deficient mice. These data indicate that control of mCMV-specific CD8+ T-cell expansion and contraction is more complex than anticipated and, despite the role of Prf or IFN-γ in controlling viral replication, a full program of T-cell expansion and contraction can occur in their absence.

scholarly journals Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice

2009 ◽  
Vol 83 (17) ◽  
pp. 8463-8469 ◽  
Author(s):  
Tatsuo Kanda ◽  
Robert Steele ◽  
Ranjit Ray ◽  
Ratna B. Ray
Keyword(s):  
Transcription Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Time Course ◽  
Nonstructural Protein ◽  
Gamma Interferon ◽  
Tnf Α ◽  
Ifn Γ ◽  
And Control ◽  
Nonstructural Protein 5A

ABSTRACT Hepatitis C virus (HCV) utilizes strategies to suppress or evade the host immune response for establishment of persistent infection. We have shown previously that HCV nonstructural protein 5A (NS5A) impairs tumor necrosis factor alpha (TNF-α)-mediated apoptosis. In this study, we have examined the immunomodulatory role of HCV NS5A protein in transgenic mouse (NS5A-Tg) liver when mice were challenged with an unrelated hepatotropic adenovirus as a nonspecific stimulus. Hepatotropic adenovirus was introduced intravenously into NS5A-Tg mice and control mice, and virus clearance from liver was compared over a time course of 3 weeks. The differential mRNA expression levels of 84 cytokine-related genes, signal pathway molecules, transcription factors, and cell surface molecules were determined using real-time reverse transcription-PCR array. NS5A-Tg mice failed to clear adenovirus from liver up to 3 weeks postinfection while control mice cleared virus within 1 to 2 weeks. Subsequent study revealed that gamma interferon (IFN-γ) expression is inhibited at both the mRNA and protein levels in NS5A-Tg mice, and an inverse expression of transcription factors Gata-3 and Tbx21 is observed. However, TNF-α mRNA and protein expression were elevated in both NS5A-Tg and control mice. Together, our results suggested that HCV NS5A acts as an immunomodulator by inhibiting IFN-γ production and may play an important role toward establishment of chronic HCV infection.

scholarly journals Clinical and Diagnostic Developments of a Gamma Interferon Release Assay for Use in Bovine Tuberculosis Control Programs

2013 ◽  
Vol 20 (12) ◽  
pp. 1827-1835 ◽  
Author(s):  
K. E. Bass ◽  
B. J. Nonnecke ◽  
M. V. Palmer ◽  
T. C. Thacker ◽  
R. Hardegger ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Second Generation ◽  
Gamma Interferon ◽  
Tuberculosis Control ◽  
Content Type ◽  
Control Programs ◽  
Release Assay ◽  
Ifn Γ ◽  
First And Second Generation ◽  
And Control

ABSTRACTCurrently, the Bovigam assay is used as an official supplemental test within bovine tuberculosis control programs. The objectives of the present study were to evaluate twoMycobacterium bovis-specific peptide cocktails and purified protein derivatives (PPDs) from two sources, liquid and lyophilized antigen preparations. PPDs and peptide cocktails were also used for comparison of a second-generation gamma interferon (IFN-γ) release assay kit with the currently licensed first-generation kit (Bovigam; Prionics AG). Three strains ofM. boviswere used for experimental challenge:M. bovis95-1315,M. bovisRavenel, andM. bovis10-7428. Additionally, samples from a tuberculosis-affected herd (i.e., naturally infected) were evaluated. Robust responses to both peptide cocktails, HP (PC-HP) and ESAT-6/CFP10 (PC-EC), and the PPDs were elicited as early as 3 weeks after challenge. Only minor differences in responses to Commonwealth Serum Laboratories (CSL) and Lelystad PPDs were detected with samples from experimentally infected animals. For instance, responses to LelystadM. avium-derived PPD (PPDa) exceeded the respective responses to the CSL PPDa inM. bovisRavenel-infected and control animals. However, a 1:4 dilution of stimulated plasma demonstrated greater separation of PPDb from PPDa responses (i.e., PPDb minus PPDa) with the use of Lelystad PPDs, suggesting that Lelystad PPDs provide greater diagnostic sensitivity than CSL PPDs. The responses to lyophilized and liquid antigen preparations did not differ. Responses detected with first- and second-generation IFN-γ release assay kits (Bovigam) did not differ throughout the study. In conclusion, antigens may be stored in a lyophilized state without loss in potency, PC-HP and PC-EC are dependable biomarkers for aiding in the detection of bovine tuberculosis, and second-generation Bovigam kits are comparable to currently used kits.

scholarly journals Kinetics of a Gamma Interferon Response: Expression and Assembly of CIITA Promoter IV and Inhibition by Methylation

2002 ◽  
Vol 22 (13) ◽  
pp. 4781-4791 ◽  
Author(s):  
Ann C. Morris ◽  
Guy W. Beresford ◽  
Myesha R. Mooney ◽  
Jeremy M. Boss
Keyword(s):  
Gene Expression ◽  
Chromatin Immunoprecipitation ◽  
Chromatin Modification ◽  
Gamma Interferon ◽  
Interferon Response ◽  
Regulatory Factor ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Response Expression ◽  
Kinetics Of

ABSTRACT Chromatin immunoprecipitation assays were employed to assess the kinetics of transcription factor assembly and histone modifications that occur during gamma interferon (IFN-γ) induction of CIITA gene expression. CIITA is the master regulator of major histocompatibility complex class II transcription. Promoter IV (PIV), the major IFN-γ responsive promoter for CIITA expression, requires both STAT1 and IFN regulatory factor 1 (IRF-1) for induction by IFN-γ. STAT1 binding to PIV was detected first and was accompanied by a modest acetylation of histones H3 and H4 that were associated with the region. Despite these changes, which occurred within 30 min of IFN-γ treatment, CIITA mRNA was not detected until IRF-1 protein was synthesized and bound to its site, a process that required >120 min. In contrast to these events, fetal trophoblast-like cell lines, which are refractory to CIITA induction by IFN-γ, failed to assemble the above factors or modify their chromatin, suggesting that accessibility to the promoter is blocked. Bisulfite sequencing of PIV showed strong hypermethylation of PIV, providing a link between methylation, chromatin structure, and factor binding. Together, this analysis provides a kinetic view of the activation of the CIITA gene in response to IFN-γ and shows that regulatory factor assembly, chromatin modification, and gene expression proceed in discrete steps.

scholarly journals Interleukin-4 and Transforming Growth Factor β Have Opposing Regulatory Effects on Gamma Interferon-Mediated Inhibition of Cryptosporidium parvum Reproduction

2003 ◽  
Vol 71 (8) ◽  
pp. 4580-4585 ◽  
Author(s):  
I.-Sarah Lean ◽  
Stuart A. C. McDonald ◽  
Mona Bajaj-Elliott ◽  
Richard C. G. Pollok ◽  
Michael J. G. Farthing ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cryptosporidium Parvum ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Effector Cells ◽  
Ifn Γ

ABSTRACT It was shown previously that enterocytes activated by gamma interferon (IFN-γ) are efficient effector cells in the killing of Cryptosporidium parvum. How this function is regulated is not clearly understood, but transforming growth factor β (TGF-β) and the Th2 regulatory cytokines may play a role. Using an in vitro cell culture system, we investigated how the key regulatory cytokines interleukin-4 (IL-4), IL-10, IL-13, and TGF-β might modulate the effect of IFN-γ in inducing resistance to infection in enterocyte cell lines. The results showed that TGF-β can abolish the inhibitory effect on C. parvum development and that neither IL-13 nor IL-10 influenced the action of IFN-γ. In contrast, IL-4 cooperated with low concentrations of IFN-γ (1 and 10 U/ml) to enhance parasite killing. One mechanism that appeared to be involved in the combined activity of IFN-γ and IL-4 was intracellular Fe2+ deprivation, but induction of nitric oxide production was not involved. In one cell line, the extents and durations of phosphorylation of STAT1, a transcription factor involved in IFN-γ signaling, were similar when cells were stimulated with IFN-γ alone and with IFN-γ and IL-4γ, suggesting that the cooperative effect of the cytokines was not related to STAT1 activation. The effects of the presence of TGF-β and IL-4 on IFN-γ function did not appear to involve any alteration in the level of expression of IFN-γ receptors.

Sign in / Sign up

Export Citation Format

Share Document