Leukocyte migration in the interstitial space of non-lymphoid organs

Weninger, Wolfgang; Biro, Maté; Jain, Rohit

doi:10.1038/nri3641

Cited by 182 publications

(167 citation statements)

References 136 publications

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“…In turn, neutrophil apoptosis during infection is essential to convey "eat-me" signals that attract inflammatory monocytes to the site of inflammation (80). BI-1 also plays a role in actin polymerization and cell adhesion (81), mechanisms that are tightly regulated during leukocyte egress and extravasation (82). The second most significant gene product, ITGA5 (a5), is the a subunit of the fibronectin receptor (a5b1) expressed on various immune cells, mediating binding to fibronectin and extravasation toward infectious stimulus (83)(84)(85).…”

Section: Discussionmentioning

confidence: 99%

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

Radovanovic

Leung

Iliescu

et al. 2014

The Journal of Immunology

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In the immunocompromised host, invasive infection with the fungal pathogen Candida albicans is associated with high morbidity and mortality. Sporadic cases in otherwise normal individuals are rare, and they are thought to be associated with genetic predisposition. Using a mouse model of systemic infection with C. albicans, we identified the SM/J mouse strain as unusually susceptible to infection. Genetic linkage studies in informative [C57BL/6JxSM/J]F2 mice identified a major locus on distal chromosome 15, given the appellation Carg5, that regulates C. albicans replication in SM/J mice. Cellular and molecular immunophenotyping experiments, as well as functional studies in purified cell populations from SM/J and C57BL/6J, and in [C57BL/6JxSM/J]F2 mice fixed for homozygous or heterozygous Carg5 alleles, indicate that Carg5-regulated susceptibility in SM/J is associated with a complex defect in the myeloid compartment of these mice. SM/J neutrophils express lower levels of Ly6G, and importantly, they show significantly reduced production of reactive oxygen species in response to stimulation with fMLF and PMA. Likewise, CD11b+Ly6G−Ly6Chi inflammatory monocytes were present at lower levels in the blood of infected SM/J, recruited less efficiently at the site of infection, and displayed blunted oxidative burst. Studies in F2 mice establish strong correlations between Carg5 alleles, Ly6G expression, production of serum CCL2 (MCP-1), and susceptibility to C. albicans. Genomic DNA sequencing of chromatin immunoprecipitated for myeloid proinflammatory transcription factors IRF1, IRF8, STAT1 and NF-κB, as well as RNA sequencing, were used to develop a “myeloid inflammatory score” and systematically analyze and prioritize potential candidate genes in the Carg5 interval.

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Section: Discussionmentioning

confidence: 99%

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

Radovanovic

Leung

Iliescu

et al. 2014

The Journal of Immunology

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“…In the embryo, hematopoietic stem cells, immature neurons, and PGCs migrate as single cells from their point of specification to their final location (Chiquoine, 1954;Berry and Rogers, 1965;Johnson and Moore, 1975;Forrester and Garriga, 1997). In adult homeostasis, leukocytes survey the body for wounding and infection by migrating through various tissues and the vasculature (de Bruyn, 1946;Miller et al, 2003;Weninger et al, 2014). In cancer, metastatic cells move out of the primary tumor by hijacking components of the migratory network to colonize new sites around the body (Clark and Vignjevic, 2015).…”

Section: Single Cell Migrationmentioning

confidence: 99%

“…This process occurs over approximately 1.5 days, from stages 9 to 17 of embryonic development. Gonadal ridges mesoderm (Nakamura et al, 2007) and the similarities in movement with leukocytes during inflammation (reviewed in Weninger et al, 2014) suggest that migration through the endothelium and within the mesoderm is an active process. In situ hybridization revealed high levels of SDF1 expression in the mesodermal tissues of later chick PGC migration and concordant expression of CXCR4 on the germ cells (Stebler et al, 2004).…”

Section: Conservation Of Primordial Germ Cell Migrationmentioning

confidence: 99%

Primordial germ cell migration and the Wnt signaling pathway

Cantu

Laird

2017

Anim Reprod

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A critical step in the development of gametes is the migration of their primordial germ cell (PGC) precursors to the forming gonads. Although the location and mode of PGC specification differs between organisms, the formation of a committed germline before organogenesis creates a need for migration through the growing embryo in order to reach the site of gonadogenesis. Failure of PGC migration can, in many cases, compromise fertility or conversely lead to the formation of teratomas in sites outside of the gonad. Here we review the mechanism of migration employed by PGCs and compare the timing and routes across several model organisms. We summarize recent work on the role of the Wnt signaling pathway in cell migration and the lineage specific function in PGCs, mainly through the ligand Wnt5a and its receptor Ror2.

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“…The neutrophils play a critical role in the swift clearance of infection. Rapid recruitment of neutrophils at the site of infection (Miller, 2013), engulfment of microbes followed by apoptosis and the occurrence of leukocyte extravasations mainly in the post-capillary venules where haemodynamic shear forces are minimum (Weninger et al, 2014), may help promote clearance of infection. Here we measure the composition and load of few respiratory microbes in FWS, as well as the virulence potential of desquamated human scalp cells.…”

Section: Introductionmentioning

confidence: 99%

Genomic Signature of Respiratory Microbes on Human Scalp Epithelia

Paul¹,

Mishra²,

Chhabra³

et al. 2015

American Journal of Immunology

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Abstract:Despite overlap between habitats occupied by diverse Airborne Respiratory Microbes (ARM), the airway epithelium is known for respiratory microbe infections, human scalp epithelium is undocumented. Analogous to airways epithelium, the scalp epithelium is vulnerable to infection by dormant variants of sensitive microbes that underlie many chronic and relapsing diseases, difficult to eradicate by conventional antibiotics and challenged our ability to treat chronic infection. Hence comprehensive understanding of scalp epithelium ARM load, its disposal and impact on the host, as well as the environment, remains to be defined; we need to know the portals of entry and the virulence potential of ARM in determining the impact on human health and well beings. Here we investigate the genomic signature of diverse ARM in inflammatory scalp programmed for desquamation. Spatial analysis of Mycobacterium tuberculosis (Mtb), Chlamydophila pnumoniae (Cp), Escherichia coli (E. coli), Respiratory Syncytial virus strain A/B (RSVA/RSVB) and Influenza virus (H1N1) in the Flakes of White Scales (FWS) from the hair bearing areas of the scalp by quantitative (q) PCR reveals flux of microbes ranging from ~106 to 10 8 copies/ng FWS-DNA. Mtb and 16SrRNA identity reaffirmed by amplicon sequencing. Absence of microbe gene expression signatures in FWS negates the presence of viable ARM, absence of E. coli adhesin mRNA indicates habitat rejection in coculture of epithelial cells and E. coli JM107 and absence of H1N1 hemaglutinin1 (H1) mRNA in FWS rules out canonical binding and downstream infection of neighboring cell by H1N1. We conclude that desquamated epithelium, in addition to Malassezia sp, bear diverse genomic signatures of non-virulent respiratory microbes, suggest an undefined portal of entry, helps in clearance of microbes and possess minimum risk of re-infection to neighboring cells and subjects.

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Leukocyte migration in the interstitial space of non-lymphoid organs

Cited by 182 publications

References 136 publications

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

Primordial germ cell migration and the Wnt signaling pathway

Genomic Signature of Respiratory Microbes on Human Scalp Epithelia

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