Modulation of adaptive and innate immune responses by myeloid cells during malaria

Abstract

Plasmodium chabaudi chabaudi AS infection 4.2.1. Absence of Clec9A + DCs dysregulates induction of Th1 proinflammatory responses and T effector polyfunctionality in PccAS infection 4.2.2. An intact innate immune compartment compensates for polyfunctional proinflammatory responses in the absence of Clec9A + DCs 4.2.3. Germinal center reactions, B-cell responses and Ig production are not abrogated in absence of Clec9A + DCs 4.2.4. Absence of Clec9A + DCs diminishes Th1-like effector TFH and proinflammatory signals required for class switch recombination to more protective Th1 IgG2 and IgG3 4.2.5. The Th1-TFH relationship conundrum 4.2.6. Clec9A + DC deficiency results in persistent T effector and memory precursor impairment during recrudescent PccAS infection 4.3. Caveats and limitations in the Clec9A-DTR PccAS infection model 4.4. Organ-specific tissue-resident macrophages are replenished with different kinetics during acute Plasmodium yoelii infection 4.4.1. Emptied embryonically-seeded TRMØ niches in spleen and liver are partially replenished by BM-derived monocytic progenitors that differentiate into stable, bona fide TRMØs 4.4.2. Depleted lung alveolar MØs almost exclusively self-renew 8 with negligible input from BM-derived circulatory monocytes during acute Py1.1GFP infection 4.5. Rapidly-responding Ly6C hi inflammatory monocytes and monocyte-derived MØs massively infiltrate afflicted tissues and contribute to Py1.1GFP clearance 4.5.1. Ly6C hi inflammatory monocytes rapidly and massively infiltrate organs upon Py1.1GFP infection 4.5.2. Concerted efforts of FrII inflammatory monocytes and monocyte-derived / other tissue-resident MØs in resolution of Py1.1GFP infection 4.6. BM monocyte-derived MØs are phenotypically and transcriptionally similar to bona fide embryonic tissue-resident MØs 4.7. Plasmodium infection as a new precedent for the general mechanism of beneficial cell suicide 5. Summary 6. Significance of studies on current malaria immunological research 6.1. Clec9A + DCs and their roles in anti-Plasmodium immunity 6.2. Tissue-resident MØ repopulation kinetics during Plasmodium infection 6.3. Concluding remarks 7. Appendix 7.1. Cell phenotype profile 7.2. List of antibody panels 7.3. Supplementary figures 8. References 9. Author's publication(s) 10. Oral and poster presentations 9 Abbreviations ACT Artemisinin-based combination therapy ADCI Antibody-dependent cellular inhibition APC Antigen presenting cells AGM Aorta-gonad-mesonephros AMØ Alveolar macrophage Baf8 Basic leucine zipper ATF-like transcription factor BBB Blood-brain barrier BM Bone marrow BMEM Memory B-cells CD Cluster of differentiation cDC Conventional dendritic cells cKit Tyrosine-protein kinase Kit CSF-1/MCF-1 Colony stimulating factor 1 CCL CC motif chemokine ligand CCR CC chemokine receptor CDP Common dendritic progenitor CLEC9A C-type lectin receptor 9A CMP Common myeloid progenitor CMoP Common monocyte progenitor CTL Cytotoxic T lymphocytes CX3CR1 CX3C chemokine receptor 1 CXCR5 C-X-C chemokine receptor type 5 DNA Deoxyribonucleic ...