Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria

Tukwasibwe, Stephen; Nakimuli, Annettee; Traherne, James A.; Chazara, Olympe; Jayaraman, Jyothi; Trowsdale, John; Moffett, Ashley; Jagannathan, Prasanna; Rosenthal, Philip J.; Cose, Stephen; Colucci, Francesco

doi:10.1038/s41423-020-0482-z

Cited by 25 publications

(15 citation statements)

References 116 publications

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“…In addition, Ab-dependent NK cell cytotoxicity towards IEs in malaria-exposed individuals can inhibit P. falciparum growth 31 . Furthermore, adaptive NK cells, a sub-population of differentiated specialized NK cells, were associated with lower parasitemia and protection against malaria infection through enhanced ADCC response to IEs in the presence of naturally acquired Abs from malaria-resistant individuals 32 , 65 . The potential of NK cell-mediated ADCC to protect individuals against placental malaria is still to be determined.…”

Section: Discussionmentioning

confidence: 99%

Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Damelang

Aitken

Hasang

et al. 2021

Sci Rep

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Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.

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Section: Discussionmentioning

confidence: 99%

Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Damelang

Aitken

Hasang

et al. 2021

Sci Rep

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“… 119 , 120 NK cells contribute significantly to immune responses to malaria. 121 , 122 Human pbNK cells form conjugates with infected RBC and lyse them via ADCC. 123 , 124 Co-incubation of human PBMCs with live P. falciparum erythrocytic schizonts induced IFN-ɣ production and more than 50% of IFN-ɣ + cells were pbNK cells.…”

Section: Major Infections During Pregnancy: Torch (Toxoplasmosis Other Agents Rubella Cytomegalovirus Herpes Simplex)mentioning

confidence: 99%

Maternal natural killer cells at the intersection between reproduction and mucosal immunity

Shmeleva

Colucci

2021

Mucosal Immunology

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Many maternal immune cells populate the decidua, which is the mucosal lining of the uterus transformed during pregnancy. Here, abundant natural killer (NK) cells and macrophages help the uterine vasculature adapt to fetal demands for gas and nutrients, thereby supporting fetal growth. Fetal trophoblast cells budding off the forming placenta and invading deep into maternal tissues come into contact with these and other immune cells. Besides their homeostatic functions, decidual NK cells can respond to pathogens during infection, but in doing so, they may become conflicted between destroying the invader and sustaining fetoplacental growth. We review how maternal NK cells balance their double duty both in the local microenvironment of the uterus and systemically, during toxoplasmosis, influenza, cytomegalovirus, malaria and other infections that threat pregnancy. We also discuss recent developments in the understanding of NK-cell responses to SARS-Cov-2 infection and the possible dangers of COVID-19 during pregnancy.

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“…In particular, it is possible that these clusters are hot spots for gene birth and death, which could provide the mechanism for our observations of intra-specific gene content variation. Although the diversification dynamics of these gene clusters remain unknown, inter-individual variation in gene content would provide a wider degree of protection to the next unknown pathogen (Uhrberg et al 2002; Vilches and Parham 2002; Tukwasibwe et al 2020) that at the level of meta-populations could mitigate the impact of novel pathogens during such evolutionary events. As we expand our ability to move detailed comparative genomic studies from the root of the teleost phylogeny to the tips, testing how such shifts in ecological opportunities often associated with the diversification of lineages (Near et al 2013; Berv and Field 2018) and key ecological phenotypes (Salzburger 2018; Daane et al 2019) has shaped the genomic basis of ray-finned fish immunity represents an exciting research frontier.…”

Section: Summary: Considering Dicps and Nitrs In The Context Of The Tgdmentioning

confidence: 99%

Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system

Dornburg¹,

Wcisel

Zapfe³

et al. 2021

Preprint

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Over 99% of ray-finned fishes (Actinopterygii) are teleosts, a clade that comprises half of all living vertebrates that have diversified across virtually all fresh and saltwater ecosystems. This ecological diversity raises the question of how the immunogenetic diversity required to persist under heterogeneous pathogen pressures evolved. The teleost genome duplication (TGD) has been hypothesized as the evolutionary event that provided the genomic substrate for rapid genomic evolution and innovation. However, studies of putative teleost-specific innate immune receptors have been largely limited to comparisons either among teleosts or between teleosts and distantly related vertebrate clades such as tetrapods. Here we describe and characterize the receptor diversity of two clustered innate immune gene families in the teleost sister lineage: Holostei (bowfin and gars). Using genomic and transcriptomic data, we provide a detailed investigation of the phylogenetic history and conserved synteny of gene clusters encoding diverse immunoglobulin domain-containing proteins (DICPs) and novel immune-type receptors (NITRs). These data demonstrate an ancient linkage of DICPs to the major histocompatibility complex (MHC) and reveal an evolutionary origin of NITR variable-joining (VJ) exons that predate the TGD by at least 50 million years. Further characterizing the receptor diversity of Holostean DICPs and NITRs illuminates a sequence diversity that rivals the diversity of these innate immune receptor families in many teleosts. Taken together, our findings provide important historical context for the evolution of these gene families that challenge prevailing expectations concerning the consequences of the TGD during actinopterygiian evolution.

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Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria

Cited by 25 publications

References 116 publications

Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Maternal natural killer cells at the intersection between reproduction and mucosal immunity

Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system

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