Gr-1high Polymorphonuclear Leukocytes and NK Cells Act via IL-15 to Clear Intracellular <i>Haemophilus influenzae</i> in Experimental Murine Peritonitis and Pneumonia

Miyazaki, Shunichi; Ishikawa, Fumio; Shimizu, Keizo; Ubagai, Tsuneyuki; Edelstein, Paul H.; Yamaguchi, Keizo

doi:10.4049/jimmunol.179.8.5407

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…5). This is consistent with the finding that neutrophils are involved in the activation and maintenance of NK cells during influenza virus infection (62) and with neutrophil cytokines such as IL-15 promoting survival and trafficking to sites of infection (63)(64)(65). Moreover, activated NK cells express high concentrations of IFN-␥ after interaction with NKp46 and sugar residues expressed on the surface of the HA protein (66).…”

Section: Resultssupporting

confidence: 78%

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Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

Dlugolenski

Jones

Howerth

et al. 2015

J Virol

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Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of ␣2,3-or ␣2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. IMPORTANCEInfluenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance. E ach year, influenza A viruses (IAVs) cause epidemics with high morbidity and some mortality in humans (1). In avian species, IAV infection generally is associated with mild disease, and it is only when the virus crosses species barriers that pathogenic traits are attributed to infection (2). IAV is frequently associated with spillover events, as numerous species are susceptible to IAV. Often, reassortment of IAV leads to a subtype or variant that has not previously infected humans, and as the virus adapts and is transmitted more easily, a pandemic event may loom. IAV is the cause of Ͼ30,000 deaths in the United States and Ͼ500,000 deaths worldwide annually (3). In the past century, four IAV pandemics have occurred, i.e....

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Section: Resultssupporting

confidence: 78%

“…Neutrophil-depleted mice have impaired NK cell maturation exhibiting hyperproliferation and weak survival (80). Neutrophils also express high levels of IL-15, which promotes NK cell activation (63)(64)(65). Early recruitment of neutrophils by PA likely mediates the activation and maintenance of NK cells observed at 4 days p.i.…”

Section: Discussionmentioning

confidence: 99%

Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

Dlugolenski

Jones

Howerth

et al. 2015

J Virol

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“…They showed that bacterial counts were higher in blood, liver, and peritoneum after NK cell depletion at 4 h after CLP, but that bacterial numbers were not different between control and NK cell-deficient mice at 18 h, the time point used in our studies. Other reports have shown that NK cells contribute to bacterial clearance in experimental models of E. coli, H. influenza, and L. monocytogenes infection, among others (31)(32). Therefore, NK cells appear to be an important component of the host response to infection in many circumstances.…”

Section: Discussionmentioning

confidence: 99%

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Etogo

Nunez

Chen

et al. 2008

The Journal of Immunology

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Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80+GR-1−) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.

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“…We employed four-color FACS to distinguish different immunocyte populations: CD45 as a marker for nucleated hematopoietic cells (31), CD11b as a marker for macrophage/microglia (32), F4/80 as a mature macrophage marker (33), and GR1 as a neutrophil marker in peripheral organs (34). The splenocytes isolated from control animals contained 11.05 Ϯ 1.96% CD45 ϩ CD11b high macrophages/granulocytes of all CD45 ϩ lymphocytes (Fig.…”

Section: Sox2mentioning

confidence: 99%

Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis

Yin¹,

Liu

Yang

et al. 2016

Journal of Biological Chemistry

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CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation of Cul4a in mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4b germ cell-specific conditional knock-out (Cul4b Protein degradation via the ubiquitin-proteasome system plays a critical role during mammalian spermatogenesis. Timely removal of outlived proteins is crucial to ensure progression through different phases of spermatogenesis including mitotic, meiotic divisions, and postmeiotic morphogenesis. The ubiquitin-proteasome system selects its targets via a group of E3 ubiquitin ligases, which upon interaction with E2 ubiquitin-conjugating enzymes tag substrates for proteasomal degradation by the 26S proteasome. The largest mammalian E3 ligase family is the CRL (cullin-RING finger ubiquitin ligase) family, which includes eight members. Each cullin family member serves as a molecular scaffold and forms an E3 ligase complex with substrate-recruiting receptors and a linker protein (1). The Cul4b gene, located on the X chromosome, shares extensive sequence homology and functional redundancy with the other CRL4 family member, Cul4a. Both proteins employ DDB1 (DNA damage-binding protein 1) as the linker protein, which in turn recruits common or distinct DDB1-CUL4 associated factors for substrate binding. The DDB1-CUL4-mediated protein modification/degradation is involved in critical cellular processes including DNA replication, DNA repair, cell cycle control, and histone modifications (2).Male infertility accounts for ϳ40 -50% of infertility cases in humans (3, 4). Many factors contribute to male infertility; however, the vast majority of male infertility cases are associated with oligozoospermia (decreased sperm number), asthenozoospermia (reduced sperm motility), and/or teratozoospermia (abnormal sperm morphology). In the mammalian testis, a single pluripotent spermatogonial stem cell (SSC) 2 undergoes several rounds of mitotic divisions followed by meiotic divisions and complex postmeiotic morphogenesis, eventually giving rise to a cohort of mature spermatozoa. We have previously reported that the CRL4 proteins exhibited complementary expression patterns in adult mouse testis, where CUL4A was predominantly detected in primary spermatocytes, whereas CUL4B was highly expressed in Sertoli cells, spermatogonia, and spermatids (5). The absence of CUL4B in spermatocytes is likely due to meiotic sex chromosome inactivation, a transient X chromosome inactivation caused by sex chromosome condensation and subsequent gene silencing (6). However, the

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Gr-1high Polymorphonuclear Leukocytes and NK Cells Act via IL-15 to Clear Intracellular Haemophilus influenzae in Experimental Murine Peritonitis and Pneumonia

Cited by 23 publications

References 48 publications

Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis

Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis

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