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Macrophages pulsed with Streptococcus pneumoniae elicit a T cell-dependent antibody response upon transfer into naive
Sam Vasilevsky1, Jesus Colino, Roman Puliaev
1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Abstract:
Macrophages are less effective than DC at priming naive CD4(+) T cells, suggesting that DC are unique in initiating T cell-dependent Ab responses. We compared the ability of DC and macrophages, pulsed in vitro with Streptococcus pneumoniae, to elicit protein- and polysaccharide-specific Ig isotype production upon adoptive transfer into naive mice. S. pneumoniae-activated DC secreted more proinflammatory and anti-inflammatory cytokines, expressed higher levels of surface MHC class II and CD40, and presented S. pneumoniae or recombinant pneumococcal surface protein A (PspA) to a PspA-specific T hybridoma more efficiently than macrophages. However, upon adoptive transfer into naive mice, S. pneumoniae-pulsed macrophages elicited an IgM or IgG anti-PspA and anti-polysaccharide response comparable in serum titers and IgG isotype distribution to that induced by DC. The IgG anti-PspA response, in contrast to the IgG anti-polysaccharide, to S. pneumoniae-pulsed macrophages was T cell-dependent. S. pneumoniae-pulsed macrophages that were paraformaldehyde-fixed before transfer or lacking expression of MHC class II or CD40 were highly defective in eliciting an anti-PspA response, although the anti-polysaccharide response was largely unaffected. To our knowledge, these data are the first to indicate that macrophages can play an active role in the induction of a T cell-dependent humoral immune response in a naive host.
Insights
Macrophages can initiate T cell-dependent antibody responses, challenging the long-held belief that only dendritic cells (DCs) possess this unique capability. This study reveals macrophages
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are traditionally considered unique in initiating T cell-dependent antibody (Ab) responses.
- Macrophages are generally viewed as less effective than DCs in priming naive CD4(+) T cells.
Purpose of the Study:
- To compare the capacity of DCs and macrophages to elicit T cell-dependent and T cell-independent humoral immune responses.
- To investigate the role of antigen presentation by macrophages in initiating adaptive immunity.
Main Methods:
- In vitro pulsing of DCs and macrophages with Streptococcus pneumoniae.
- Adoptive transfer of pulsed cells into naive mice.
- Analysis of anti-pneumococcal protein A (PspA) and polysaccharide-specific Ig isotype production.
- Assessment of T cell dependency by using paraformaldehyde-fixed or MHC class II/CD40-deficient macrophages.
Main Results:
- S. pneumoniae-pulsed macrophages induced IgM and IgG responses against PspA and polysaccharides comparable to DCs.
- The IgG anti-PspA response elicited by macrophages was T cell-dependent.
- Macrophage antigen presentation via MHC class II and CD40 was crucial for the T cell-dependent anti-PspA response, but not the anti-polysaccharide response.
Conclusions:
- Macrophages can actively induce T cell-dependent humoral immune responses in a naive host.
- This finding challenges the established view of DCs as the sole initiators of such responses.
- Macrophages play a significant role in initiating adaptive immunity, particularly T cell-dependent antibody production.
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