Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with Mycobacterium bovis (BCG) or injection of killed Corynebacterium parvum protected some strain B6D2 F1 (C57BL/6xDBA/2) mice but did not protect strain ICR or A mice from lethal challenge with Plasmodium berghei strain NYU-2. B6D2 mice were not protected against challenges delivered immediately after intravenous injection of these materials, but rather protection developed by day 7 and persisted through at least day 84. Infections in protected mice progressed to about 10% parasitemia in parallel with infections initiated with the same inoculum in untreated controls. However, infections in most of the protected mice were cleared subsequently, whereas infections in untreated controls were uniformly fatal. A small number of treated mice developed protracted high-level erythrocytic infections, which led to markedly delayed death. BCG-infected mice which survived P. berghei infections had a factor in their sera which protected passively immunized recipients from P. berghei. BCG-infected mice passively immunized with protective serum controlled P. berghei infections better than normal mice given the same amount of the same serum and challenged with the same P. berghei inoculum. The capacity of BCG-infected B6D2 mice to resist P. berghei infection was not directly related to the pattern of growth of BCG, to the degree of splenomegaly, or to the level of activation of macrophages (measured as microbicidal capacity) caused by BCG infection. Therefore, I concluded that (i) BCG infection or injection of killed C. parvum altered the immunological potential of B6D2 mice in such a way as to allow the production of measurable levels of a protective humoral factor in response to infection with P. berghei; (ii) BCG infection caused the generation of a capacity which, when expressed in the presence of immune serum, provided an anti-P. berghei capacity which was superior to that provided by BCG infection alone or immune serum in the absence of BCG infection; and (iii) not all strains of mice could be protected from P. berghei by BCG or C. parvum injection.
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PMID:Host defenses in murine malaria: nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation. 702 24

It has previously been reported that inhibition of delayed-type hypersensitivity-mediating functions of T cells during mycobacterial infection in mice is haplotype dependent. In the present study, we show that Mycobacterium bovis BCG infection induced, in susceptible C57BL/6 and BALB/c mice but not in resistant C3H/HeJ and DBA/2 mice, an important splenomegaly. An in vitro defect in T-cell proliferation in response to T-cell receptor (TCR) stimulation with mitogens or anti-CD3 antibodies was associated with enhanced levels of CD4(+) and CD8(+) T-cell apoptosis in susceptible but not in resistant mice 2 weeks after infection. Further investigations of C57BL/6 and C3H/HeJ mice revealed that in vivo splenomegaly was associated with destruction of the lymphoid tissue architecture, liver cellular infiltrates, and increased numbers of apoptotic cells in both spleen and liver tissue sections. Infection of C57BL/6 mice but not of C3H/HeJ mice induced massive production of tumor necrosis factor alpha (TNF-alpha) in serum, as well as an increase in Fas and Fas ligand (FasL) expression in T cells. In vitro addition of neutralizing anti-TNF-alpha antibodies led to a significant reduction in CD3-induced T-cell apoptosis of both CD4(+) and CD8(+) T cells of C57BL/6 mice, while the blockade of Fas-FasL interactions reduced apoptosis only in CD4(+) but not in CD8(+) T cells. Together, these results suggest that TNF-alpha and Fas-FasL interactions play a role in the activation-induced cell death (AICD) process associated with a defect in T-cell proliferation of the susceptible C57BL/6 mice. T-cell death by apoptosis may represent one of the important components of the ineffective immune response against mycobacterium-induced immunopathology in susceptible hosts.
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PMID:Ineffective cellular immune response associated with T-cell apoptosis in susceptible Mycobacterium bovis BCG-infected mice. 1085 44

Live mycobacteria have been reported to signal through several pattern recognition receptors (PRR), among them toll-like receptor 4 (TLR4) and TLR2 in vitro. Here, we investigated the role of TLR4 in host resistance to Mycobacterium bovis (BCG) infection in vivo. In vitro, macrophages of TLR4 mutant C3H/HeJ mice infected with BCG expressed lower levels of TNF than controls, and TNF release was further decreased, although not completely absent, in the absence of TLR2. In vivo, TLR4 mutant C3H/HeJ and control C3H/HeOUJ mice were infected with BCG (2 x 10(6) CFU i.v.). Both TLR4 mutant and wild-type mice were able to control the infection and survived 8 months post-BCG infection. Macrophage activation with abundant acid-fast bacilli and expression of inducible nitric oxide synthase (iNOS) and MHC class II antigens was seen in both groups of mice. However, TLR4 mutant mice experienced an arrest of body weight gain and showed signs of increased inflammation, with persistent splenomegaly, increase in granuloma number and augmented neutrophil infiltration. Infection of TLR4-deficient mice with higher doses of BCG (1 and 3 x 10(7) CFU, i.v.) increased the inflammation in spleen and liver, associated with a transient, higher bacterial load in the liver. In summary, TLR4 mutant mice show normal macrophage recruitment and activation, granuloma formation and control of the BCG infection, but this is associated with persistent inflammation. Therefore, TLR4 signaling is not essential for early control of BCG infection, but it may have a critical function in fine tuning of inflammation during chronic mycobacterial infection.
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PMID:Control of Mycobacterium bovis BCG infection with increased inflammation in TLR4-deficient mice. 1455 48