Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis

ABSTRACT To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-γ) response in the EN group, in that they increased IFN-γ production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-γ responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10.

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Differences in the Frequency of Cytokine-Producing Cells in Antigenemic and Nonantigenemic Individuals with Bancroftian Filariasis

Infection and Immunity ◽

10.1128/iai.66.4.1377-1383.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1377-1383 ◽

Cited By ~ 13

Author(s):

Adriana B. de Almeida ◽

Maria Carmelita Maia e Silva ◽

Cynthia Braga ◽

David O. Freedman

Keyword(s):

Lymphatic Filariasis ◽

Mononuclear Cells ◽

Intracellular Cytokine Staining ◽

Clinical Manifestations ◽

Wuchereria Bancrofti ◽

Interleukin 4 ◽

Bancroftian Filariasis ◽

Peripheral Blood Mononuclear ◽

Geometric Means ◽

Ifn Γ

ABSTRACT Individuals with clinical manifestations of lymphatic filariasis may be currently infected or not. Twenty-five individuals from aWuchereria bancrofti-endemic area of Brazil were classified as being asymptomatic microfilaremic individuals, antigenemic individuals with clinical filariasis, or nonantigenemic individuals with clinical filariasis. Intracellular cytokine staining of mitogen-stimulated peripheral blood mononuclear cells (PBMC) showed that the frequency of either gamma interferon (IFN-γ)- or interleukin-4 (IL-4)-producing cells was higher in the nonantigenemic individuals with clinical filariasis than in the asymptomatic microfilaremic individuals (geometric means, 22.1 versus 10.7% [P = 0.02] and 2.9 versus 1.4% [P= 0.01], respectively). When the asymptomatic microfilaremic individuals and antigenemic individuals with clinical filariasis were grouped together to constitute all actively infected individuals, the frequency of IFN-γ-producing cells was also lower than in the nonantigenemic individuals with clinical filariasis (P= 0.04). Likewise, the frequency of IL-4-producing cells in the actively infected individuals was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.02). No differences in the frequency of IFN-γ-, IL-4-, or IL-5-producing cells in purified CD4 T lymphocytes were found among the groups. These findings suggest that the presence of antigenemia, which is an indicator of current active infection, is closely associated with the frequency of IFN-γ- and IL-4-producing cells in lymphatic filariasis. The differences found in the frequency of cytokine-producing cells among the three groups appear to be due to a subset of cells other than CD4 T cells.

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Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

Helminthologia ◽

10.2478/s11687-007-0003-y ◽

2007 ◽

Vol 44 (2) ◽

pp. 47-56 ◽

Cited By ~ 2

Author(s):

J. Porubcová ◽

E. Dvorožňáková ◽

Z. Ševčíková

Keyword(s):

Immune Response ◽

Amphotericin B ◽

Echinococcus Multilocularis ◽

Proliferative Response ◽

Larval Growth ◽

Colloidal Dispersion ◽

Cell Subpopulation ◽

Th2 Immune Response ◽

Ifn Γ

AbstractThe effect of amphotericin B colloidal dispersion (ABCD) on selected immunological parameters and growth of the larval cysts in mice infected intraperitoneally with Echinococcus multilocularis protoscoleces was observed. ABCD was administered at a dose 10 mg/kg body weight twice a week from week 5 to 10 post infection (p.i.). The Echinococcus infection suppressed the proliferative response of splenic T lymphocytes to nonspecific mitogen concanavalin A throughout almost the whole course of the experiment and ABCD administration did not affect this inhibittion. The increase in the proliferative response of B lymphocytes to lipopolysaccharide was found in infected mice with ABCD treatment from week 6 to 10 p.i. ABCD induced a significant rise of the splenic CD4 T cell subpopulation in infected mice only on week 6 p.i. The CD8 T subpopulation was not influenced by the therapy. The level of serum Th1 cytokine IFN-γ in infected and ABCD treated mice was elevated only at week 8 p.i., while the level of serum Th2 cytokine IL-5 was not influenced by the therapy. The ABCD treatment inhibited the IFN-γ production by splenocytes in vitro from week 6 to 10 p.i. On the contrary, the IL-5 production in vitro was stimulated at weeks 8 and 12 p.i. None antiparasitic effect of ABCD on larval growth was determined.Results suggest that amphotericin B colloidal dispersion did not affect the inhibited Th1 immune response after parasite infection. On the contrary, ABCD advanced the Th2 immune response development, which allows the progressive growth of the parasite.

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Immune Response to Infection withMycobacterium ulcerans

Infection and Immunity ◽

10.1128/iai.69.3.1704-1707.2001 ◽

2001 ◽

Vol 69 (3) ◽

pp. 1704-1707 ◽

Cited By ~ 78

Author(s):

Travis M. Gooding ◽

Paul D. R. Johnson ◽

Dianne E. Campbell ◽

John A. Hayman ◽

Elizabeth L. Hartland ◽

...

Keyword(s):

Immune Response ◽

Mononuclear Cells ◽

Tuberculin Test ◽

Acid Fast Bacillus ◽

Mycobacterium Ulcerans ◽

Cell Mediated Immunity ◽

Peripheral Blood Mononuclear ◽

T Cell Anergy ◽

Skin Ulcers ◽

Ifn Γ

ABSTRACT Mycobacterium ulcerans is a slow-growing, acid-fast bacillus that causes chronic necrotizing skin ulcers known as Buruli ulcers. Previously reported information on immunity to this mycobacterium is limited. We examined immune responses to M. ulcerans and M. bovis BCG in patients with M. ulcerans disease and in 20 healthy control subjects (10 tuberculin test positive and 10 tuberculin test negative). Cell-mediated immunity was assessed by stimulating peripheral blood mononuclear cells (PBMC) with whole mycobacteria and then measuring PBMC proliferation and the production of gamma interferon (IFN-γ). Humoral immunity was assessed by immunoblotting. PBMC from all subjects showed significantly greater proliferation and IFN-γ production in response to stimulation with living mycobacteria compared with killed cells. However, PBMC from subjects with past or current M. ulcerans disease showed significantly reduced proliferation and production of IFN-γ in response to stimulation with live M. ulcerans or M. bovis than PBMC from healthy, tuberculin test-positive subjects (P < 0.001) and showed results in these assays comparable to those of tuberculin test-negative subjects (P > 0.2). Serum from 9 of 11 patients with M. ulcerans disease, but no control subject, contained antibodies to M. ulcerans. The results indicate that patients with M. ulcerans infection mount an immune response to M. ulcerans as evidenced by antibody production, but they demonstrate profound systemic T-cell anergy to mycobacterial antigens. These findings may explain some of the distinct clinical and pathological features of M. ulcerans-induced disease.

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Cytokine Profiles of Patients Infected with Mycobacterium ulcerans and Unaffected Household Contacts

Infection and Immunity ◽

10.1128/iai.70.10.5562-5567.2002 ◽

2002 ◽

Vol 70 (10) ◽

pp. 5562-5567 ◽

Cited By ~ 64

Author(s):

Travis M. Gooding ◽

Paul D. R. Johnson ◽

May Smith ◽

Andrew S. Kemp ◽

Roy M. Robins-Browne

Keyword(s):

Immune Response ◽

Mononuclear Cells ◽

Buruli Ulcer ◽

Mycobacterium Ulcerans ◽

Interleukin 4 ◽

Peripheral Blood Mononuclear ◽

Household Contacts ◽

Control Subjects ◽

Cytokine Profiles ◽

Ifn Γ

ABSTRACT Mycobacterium ulcerans, the cause of Buruli ulcer, is an environmental mycobacterium with a distinct geographic distribution. The reasons why only some individuals who are exposed to M. ulcerans develop ulcers are not known but are likely to reflect individual differences in the immune response to infections with this bacterium. In this study, we investigated cytokine profiles of peripheral blood mononuclear cells (PBMC) from 23 Buruli ulcer patients and 25 household contacts in a region of Australia where Buruli ulcer is endemic. The results showed that following stimulation with M. ulcerans or Mycobacterium bovis BCG, PBMC from Buruli ulcer patients mounted a Th2-type response, which was manifested by the production of mRNA for interleukin 4 (IL-4), IL-5, IL-6, and IL-10, whereas unaffected contacts responded mainly with the Th1 cytokines gamma interferon (IFN-γ) and IL-12. For example, mRNA for IL-4 was detected in 18 of 23 patients but in only 3 of 25 control subjects (P < 0.0001). By contrast, PBMC from 21 of 25 unaffected individuals produced IFN-γ compared with 3 of 23 patients (P < 0.0001). IFN-γ release following stimulation with mycobacteria was markedly reduced in affected subjects. Frequencies of antibodies to M. ulcerans in serum samples from affected and unaffected subjects were similar, indicating that many of the control subjects had been exposed to this bacterium. Together, these findings suggest that a Th1-type immune response to M. ulcerans may prevent the development of Buruli ulcer in people exposed to M. ulcerans, but a Th-2 response does not.

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Cellular immune response studies in bancroftian filariasis

Journal of Helminthology ◽

10.1017/s0022149x00016047 ◽

1997 ◽

Vol 71 (3) ◽

pp. 265-267 ◽

Cited By ~ 5

Author(s):

J. Regunathan ◽

K. Jayaraman ◽

P. Kaliraj

Keyword(s):

Immune Response ◽

Mononuclear Cells ◽

Genomic Library ◽

Clinical Symptoms ◽

Wuchereria Bancrofti ◽

Proliferative Index ◽

Peripheral Blood Mononuclear ◽

Immunological Responses ◽

Significant Difference ◽

Cellular Immune

AbstractAn attempt was made to identify the filarial specific antigens that are capable of inducing immune response in human filariasis. Lymphocytes were taken from three clinically defined groups living in an endemic area in Madras, namely microfilaraemic (MF) subjects with microfilariae in their blood smear without any clinical symptoms, chronic pathology (CP) individuals with lymphangitis or lymphadenitis in combination with a history of recurrent filarial fevers or lymphoedema, and endemic normals (EN) subjects without microfilariae nor any clinical symptoms of pathology. Lymphocytes from the three groups responded with no significant difference (P = 0.21) in their proliferative index to PPD and PHA, although lymphocytes from MF individuals showed significantly (P < 0.001) less proliferative index to Brugia malayi antigen (BMA) than the CP and EN subjects. This antigen specific cellular unresponsiveness seen in MF patients was not reversed by the addition of recombinant IL-lα, IL-1β, and IFN-γ, but the addition of sera from EN individuals seemed to restore this unresponsiveness (P < 0.001). The peripheral blood mononuclear cells from MF patients secreted more IL-1 in response to BMA induction than the same from CP and EN individuals. A 58 kDa recombinant protein isolated from a Wuchereria bancrofti genomic library (58 kDa) had mounted a higher proliferative response to lymphocytes from all three groups compared to BMA (P < 0.001) indicating the possible use of recombinant filarial protein to mount immunological responses in filarial patients.

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Immunization with Brucella VirB Proteins Reduces Organ Colonization in Mice through a Th1-Type Immune Response and Elicits a Similar Immune Response in Dogs

Clinical and Vaccine Immunology ◽

10.1128/cvi.00653-14 ◽

2014 ◽

Vol 22 (3) ◽

pp. 274-281 ◽

Cited By ~ 10

Author(s):

Cora N. Pollak ◽

María Magdalena Wanke ◽

Silvia M. Estein ◽

M. Victoria Delpino ◽

Norma E. Monachesi ◽

...

Keyword(s):

Immune Response ◽

Mononuclear Cells ◽

Interleukin 4 ◽

Delayed Type Hypersensitivity ◽

Peripheral Blood Mononuclear ◽

Content Type ◽

Type Iv ◽

Ifn Γ ◽

Organ Colonization

ABSTRACTVirB proteins fromBrucellaspp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice fromBrucellainfection and whether this response can be induced in the dog, a natural host forBrucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with liveBrucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals uponin vitrostimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane ofBrucellaorganisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis ofB. caniswas assessedin vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization byBrucellain mice can be also elicited in dogs.

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Modulation of Innate Cytokine Responses by Products of Helicobacter pylori

Infection and Immunity ◽

10.1128/iai.68.11.6265-6272.2000 ◽

2000 ◽

Vol 68 (11) ◽

pp. 6265-6272 ◽

Cited By ~ 59

Author(s):

Frank Meyer ◽

Keith T. Wilson ◽

Stephen P. James

Keyword(s):

Immune Response ◽

Helicobacter Pylori ◽

Lymphocyte Proliferation ◽

Mononuclear Cells ◽

Cytokine Production ◽

Peripheral Blood Mononuclear ◽

Cytokine Responses ◽

Ifn Γ ◽

H Pylori ◽

Th1 Polarization

ABSTRACT The gastric inflammatory and immune response in Helicobacter pylori infection may be due to the effect of different H. pylori products on innate immune mechanisms. The aim of this study was to determine whether bacterial components could modulate cytokine production in vitro and thus contribute to Th1 polarization of the gastric immune response observed in vivo. The effect of H. pylori recombinant urease, bacterial lysate, intact bacteria, and bacterial DNA on proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) from H. pylori-negative donors was examined as a model for innate cytokine responses. Each of the different H. pylori preparations induced gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), but not IL-2 or IL-5, production, and all but H. pylori DNA stimulated release of IL-10. Addition of anti-IL-12 antibody to cultures partially inhibited IFN-γ production. In addition, each bacterial product inhibited mitogen-stimulated IL-2 production by PBMCs and Jurkat T cells. The inhibitory effect of bacterial products on IL-2 production correlated with inhibition of mitogen-stimulated lymphocyte proliferation, although urease inhibited IL-2 production without inhibiting proliferation, suggesting that inhibition of IL-2 production alone is not sufficient to inhibit lymphocyte proliferation. The results of these studies demonstrate that Th1 polarization of the gastric immune response may be due in part to the direct effects of multiple different H. pylori components that enhance IFN-γ and IL-12 production while inhibiting both IL-2 production and cell proliferation that may be necessary for Th2 responses.

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Immune alterations in subacute sclerosing panencephalitis reflect an incompetent response to eliminate the measles virus

PLoS ONE ◽

10.1371/journal.pone.0245077 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245077

Author(s):

Sibel P. Yentür ◽

Veysi Demirbilek ◽

Candan Gurses ◽

Safa Baris ◽

Umit Kuru ◽

...

Keyword(s):

Immune Response ◽

Measles Virus ◽

Mononuclear Cells ◽

Subacute Sclerosing Panencephalitis ◽

Peripheral Blood Mononuclear ◽

T Cell Stimulation ◽

Immune Alterations ◽

Altered Immune Response ◽

Ifn Γ ◽

Specific Stimulation

In subacute sclerosing panencephalitis (SSPE) the persistence of measles virus (MeV) may be related to the altered immune response. In this study, cytokine responses of lymphocytes and monocytes were evaluated in SSPE compared to controls with non-inflammatory (NICON) and inflammatory (ICON) diseases. Patients with SSPE (n = 120), 78 patients with ICON and 63 patients with NICON were included in this study. Phenotypes of peripheral blood mononuclear cells (PBMC) have been analyzed by flow cytometry. CD3 and CD28, and S. aureus Cowan strain I (SAC) stimulated and unstimulated cells were cultured and IL-2, IL-10, IFN-γ, IL-12p40, IL-12p70 and IL-23 were detected in supernatants by ELISA. MeV peptides were used for MeV-specific stimulation and IFN-γ secretion of PBMC was measured by ELISPOT. Spontaneous and stimulated secretions of IL-10 were lower in SSPE compared to both control groups. T cell stimulation induced lower IFN-γ production than ICON group, but higher IL-2 than NICON group in SSPE. Stimulated PBMC produced lower IL-12p70 in SSPE and had decreased CD46 on the cell surface, suggesting the interaction with the virus. IFN-γ responses against MeV peptides were not prominent and similar to NICON patients. The immune response did not reveal an inflammatory activity to eliminate the virus in SSPE patients. Even IL-10 production was diminished implicating that the response is self-limited in controlling the disease.

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Immune Responses in Cutaneous Leishmaniasis: in vitro Thelper1/Thelper2 Cy-tokine Profiles Using Live Versus Killed Leishmania major

Journal of Arthropod-Borne Diseases ◽

10.18502/jad.v15i1.6491 ◽

2021 ◽

Author(s):

Akram Miramin-Mohammadi ◽

Amir Javadi ◽

Seyyed Ebrahim Eskandari ◽

Mahmood Nateghi-Rostami ◽

Ali Khamesipour

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Leishmania Major ◽

Mononuclear Cells ◽

Control Measure ◽

Peripheral Blood Mononuclear ◽

Significant Difference ◽

History Of ◽

Ifn Γ

Background: Recovery from cutaneous leishmaniasis (CL) leads to protection against further lesion development. In contrast, vaccination using killed parasites does not induce enough protection; the reason(s) is not currently known but might be related to different immune response induced against live versus killed parasites. In this study, Th1/Th2 cyto-kine profiles of CL patients were evaluated against live versus killed Leishmania major. Methods: In this study peripheral blood mononuclear cells (PBMC) of the volunteers with active CL lesion (CL), history of CL (HCL) and healthy volunteers were cultured and stimulated with live or killed Leishmania major, the superna-tants were collected and levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method. Results: The results showed that IFN-γ levels in CL patients (p< 0.001) and HCL volunteers (p< 0.005) are signifi-cantly higher when stimulated with live than stimulated with killed L. major. IFN-γ production in PBMC volunteers with CL and HCL stimulated with live or heat-killed L. major was significantly (p< 0.001) higher than in unstimulated ones. The level of IL-5 in CL patients (p< 0.005) and HCL volunteers (p< 0.001) are significantly lower when stimulated with live than killed L. major. There was no significant difference between the levels of IL-10 in PBMC stimulated with either live or killed L. major. Conclusion: It is concluded that using live Leishmania induces a stronger Th1 type of immune response which justify using leishmanization as a control measure against CL.

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Modulation of Immune Responses to Mycobacterium bovis in Cattle Depleted of WC1+ γδ T Cells

Infection and Immunity ◽

10.1128/iai.70.3.1488-1500.2002 ◽

2002 ◽

Vol 70 (3) ◽

pp. 1488-1500 ◽

Cited By ~ 65

Author(s):

Hilary E. Kennedy ◽

Michael D. Welsh ◽

David G. Bryson ◽

Joseph P. Cassidy ◽

Fiona I. Forster ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Mycobacterium Bovis ◽

Bovine Tuberculosis ◽

Γδ T Cells ◽

Interleukin 4 ◽

In Vivo Model ◽

Peripheral Blood Mononuclear ◽

Ifn Γ

ABSTRACT It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4+ T cells produce Th1 cytokines, such as gamma interferon (IFN-γ), in response to mycobacterial antigens and that the cytolytic activity of CD8+ cells toward infected macrophages is important. However, the extent and manner in which γδ T cells participate in this response remain unclear. In ruminants, γδ T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1+ γδ T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1+ γδ T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1+-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1+ γδ T cells, which become significantly activated (CD25+) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1+-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1+ γδ TCR+ cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis—a hypothesis supported by the decreased innate production of IFN-γ, which was observed in WC1+-depleted calves.

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