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Role of macrophages in the pathogenesis of experimental tick-borne encephalitis in mice
Abstract:
In vivo phagocytosis activity of macrophages (PAM) was temporarily suppressed in mice by application of a suspension of microscopic from particles. As demonstrated, a reversible block of 70% of PAM was accompanied by a marked increase of the lethality during the acute tick-borne encephalitis (TBE) virus infection. Asymptomatic persistence of TBE virus in the brain was 4 times more frequent in mice with PAM defect than in immuno-competent mice. Suppression of PAM during the first 48 hr post infection (p.i.) did not affect interaction of B-, T-lymphocytes and macrophages. Cytotoxic activity of splenocytes against TBE virus-infected mouse embryo fibroblasts (MEF) was alike irrespective of whether cytotoxic cells were collected from mice inoculated or not inoculated with microscopic iron suspension. Similarly, frequency of seroconversion did not differ in these groups of mice. Adoptively transferred peritoneal macrophages from TBE virus-infected or intact mice did not exert any protective activity. The presence of splenic macrophages was necessary neither in adoptive immunity transfer in vivo nor in cytotoxic activity of T-lymphocytes directed to virus-infected targets in vitro. It was further found that peritoneal macrophages (PM) both from TBE virus immunized and non immunized donors in the presence of antibodies to TBE virus acquired the capability to kill TBE virus-infected target cells. Antibody-dependent cytotoxicity (ADC) of macrophages was associated with population of phagocytic cels.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Suppressing macrophage phagocytosis in mice increased tick-borne encephalitis (TBE) virus lethality and asymptomatic brain persistence. However, this did not impact T-lymphocyte interactions or antibody-dependent cytotoxicity.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Macrophages play a critical role in host defense against viral infections.
- The impact of transiently suppressed macrophage phagocytosis on tick-borne encephalitis (TBE) virus infection dynamics is not fully understood.
Purpose of the Study:
- To investigate the role of in vivo phagocytosis activity of macrophages (PAM) in the host's response to TBE virus infection.
- To determine the effects of suppressed PAM on TBE virus lethality, viral persistence in the brain, and immune cell interactions.
Main Methods:
- Temporary suppression of PAM in mice using microscopic iron particles.
- Assessment of TBE virus lethality, asymptomatic brain persistence, and immune cell (B-cells, T-lymphocytes, macrophages) interactions post-infection.
- Evaluation of splenocyte cytotoxic activity and seroconversion frequency.
- Analysis of adoptively transferred peritoneal macrophages and antibody-dependent cytotoxicity (ADC) in vitro.
Main Results:
- A 70% reversible block of PAM significantly increased TBE virus lethality and the frequency of asymptomatic brain persistence.
- Suppression of PAM within the first 48 hours post-infection did not alter interactions between B-cells, T-lymphocytes, and macrophages.
- Splenocyte cytotoxic activity and seroconversion rates were unaffected by PAM suppression; adoptively transferred macrophages did not provide protection.
- Peritoneal macrophages (PM), in the presence of TBE virus antibodies, exhibited antibody-dependent cytotoxicity (ADC) against infected target cells.
Conclusions:
- Transient suppression of macrophage phagocytosis impairs the host's ability to control TBE virus infection, leading to increased severity and persistence.
- While PAM is crucial for initial infection control, T-lymphocyte responses and antibody-dependent cytotoxicity mediated by macrophages are independent of phagocytic activity.
- Antibody-dependent cytotoxicity (ADC) by macrophages is a key mechanism in controlling TBE virus infection, particularly in the presence of antibodies.