scholarly journals Role for Nitric Oxide in Hookworm-Associated Immune Suppression

2008 ◽  
Vol 76 (6) ◽  
pp. 2560-2567 ◽  
Author(s):  
Blaise Dondji ◽  
Richard D. Bungiro ◽  
Lisa M. Harrison ◽  
Jon J. Vermeire ◽  
Carlo Bifulco ◽  
...  

ABSTRACT Hookworm infection is a major cause of anemia and malnutrition in resource-poor countries. Human and animal studies suggest that infection with these intestinal nematodes is associated with impaired cellular immunity, characterized by reduced lymphocyte proliferation in response to both parasite and heterologous antigens. We report here data from studies aimed at defining mechanisms through which hookworms modulate the host cellular immune response. Splenocytes and mesenteric lymph node (MLN) cells from hamsters infected with Ancylostoma ceylanicum showed minimal proliferation in response to mitogen at days 20 and 30 postinfection (p.i.), with partial recovery noted at day 70 p.i. The proliferative capacity of enriched splenocyte T-cell preparations from infected animals following stimulation with hookworm antigens was partially restored in the presence of antigen-presenting cells from uninfected hamsters. Analysis by fluorescence-activated cell sorting revealed that hookworm infection is associated with reduced percentages of both CD4+ and surface immunoglobulin G-positive lymphocytes in the spleen and MLN cells. Splenocytes from infected hamsters also secreted more nitric oxide (NO) in culture than did those from naïve animals. Inhibition of NO secretion was associated with partial restoration of the proliferative capacity of splenocytes from infected animals in response to concanavalin A, suggesting a role for NO in mediating this effect. Together, these data demonstrate that hookworm infection is associated with impaired function of antigen-presenting cells and depletion of important lymphocyte subpopulations and also suggests a role for NO in parasite-induced immunosuppression.

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 223-230
Author(s):  
Yoshihiro Komohara ◽  
Toshiki Anami ◽  
Kenichi Asano ◽  
Yukio Fujiwara ◽  
Junji Yatsuda ◽  
...  

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell-derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages expressing CD169 play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.


1997 ◽  
Vol 175 (5) ◽  
pp. 1121-1127 ◽  
Author(s):  
Birgit Ackermann ◽  
Martin S. Staege ◽  
Angelika B. Reske‐Kunz ◽  
Hans‐Peter Dienes ◽  
Karl‐Hermann Meyer zum Büschenfelde ◽  
...  

2009 ◽  
Vol 46 (6) ◽  
pp. 1100-1108 ◽  
Author(s):  
Geneviève Lemaire ◽  
Olivier Guittet ◽  
Marie-Françoise Vesin ◽  
Michel Lepoivre ◽  
Marie-Hélène Cottet

2000 ◽  
Vol 68 (5) ◽  
pp. 2962-2970 ◽  
Author(s):  
Markus J. Maeurer ◽  
Peter Trinder ◽  
Gerhard Hommel ◽  
Wolfgang Walter ◽  
Kirsten Freitag ◽  
...  

ABSTRACT Both antigen-presenting cells and immune effector cells are required to effectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive “cross talk” between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of α/β and γ/δ T cells. Here we show that either cytokine is able to enhance survival of M. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival of M. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 toM. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response to M. tuberculosis-infected antigen-presenting cells.


Author(s):  
Yoshihiro Komohara ◽  
Toshiki Anami ◽  
Kenichi Asano ◽  
Yukio Fujiwara ◽  
Junji Yatsuda ◽  
...  

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually &lt;1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell&ndash;derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.


Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1735-1742 ◽  
Author(s):  
K. W. Annie Bang ◽  
Edwin R. Speck ◽  
Victor S. Blanchette ◽  
John Freedman ◽  
John W. Semple

Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (iNOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigen-presenting cells [APC]) from BALB/c (H-2d) mice were pulsed with allogeneic C57BL/6 (H-2b) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-γ. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and IgG2a (1933) isotypes specific for donor major histocompatibility complex (MHC) class I antigens were detected. Platelet pulsing in the presence of AMG or colchicine significantly inhibited the ability of APC to stimulate IgG alloantibodies; only 50% (P &lt; .005) and 20% (P &lt; .0001) of recipients, respectively, produced antibodies by the sixth transfusion. AMG inhibition was reversed by the addition of l-arginine, the substrate for iNOS. In contrast, pulsing in the presence of chloroquine, the proteasome inhibitory peptide MG115, or Brefeldin A enhanced APC immunity (70-100% of recipients antibody positive by the second transfusion [P &lt; .05]); these agents allowed the pulsed APC to stimulate IgG2a but inhibited IgG1 production and this correlated with a reduction in serum interleukin (IL)-4 levels. The results suggest that for donor platelet antigens to stimulate IgG alloantibodies, recipient APC use the essential generation of nitric oxide and a noncytosolic, pH-independent processing pathway, which can be exploited as an effective immunotherapy target to further inhibit alloimmunization against leukoreduced platelets.


Allergy ◽  
2002 ◽  
Vol 57 (1) ◽  
pp. 2-8 ◽  
Author(s):  
D. von Bubnoff ◽  
H. de la Salle ◽  
J. Wessendorf ◽  
S. Koch ◽  
D. Hanau ◽  
...  

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