Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract

Ruane, Darren; Brane, Lucas; Reis, Bernardo Sgarbi; Cheong, Cheolho; Poles, Jordan; Do, Yoonkyung; Zhu, Hongfa; Velinzon, Klara; Choi, Jae-Hoon; Studt, Natalie; Mayer, Lloyd; Lavelle, Ed C.; Steinman, Ralph M.; Mucida, Daniel; Mehandru, Saurabh

doi:10.1084/jem.20122762

Cited by 120 publications

(93 citation statements)

References 72 publications

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“…Thus specific DC populations and local factors result in preferential generation of IgA-producing B cells in the GALT and MLNs and imprinting of lymphocytes with the specific gut homing receptors α4β7 integrin, CCR9 and CCR10 [66,71]. In support of the idea of a common mucosal immune system, lung DCs have also been shown to be capable of imprinting a GIT homing phenotype on T cells allowing for their migration to the gut where they facilitated protection against an intestinal Salmonella infection [79]. Once primed, lymphocytes exit the PPs and the MLNs via the thoracic duct and blood and finally migrate back to the gut via homing receptors and cognate ligands expressed only in the gut tissue.…”

Section: Gut Immune Responsesmentioning

confidence: 92%

Delivery strategies to enhance oral vaccination against enteric infections

Davitt

Lavelle

2015

Advanced Drug Delivery Reviews

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133

102

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Section: Gut Immune Responsesmentioning

confidence: 92%

Delivery strategies to enhance oral vaccination against enteric infections

Davitt

Lavelle

2015

Advanced Drug Delivery Reviews

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133

102

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“…53,54 Although there have been reports of mucosal compartmentalization restricting induction of intestinal immune responses by intranasal immunization, a recent study by Ruane et al showed that intranasal immunization stimulated a 4 b 7 expression on T cells in the lung and the mediastinal lymph nodes and induced cell migration to the GI tissues. 94 This activity was mediated by lung DCs, in a process similar to that exhibited by mesenteric lymph node DCs. Consistent with this concept, DNA encoding HIV-1 gag fused to lysosome-associated membrane protein (LAMP/gag) delivered intranasally to neonatal mice was shown to elicit IgA, IgG, and IFN-c + T cell responses in the intestines.…”

Section: Intranasal Vaccinationmentioning

confidence: 94%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

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“…In fact, not only pathogenic microorganisms but also commensal and symbiont microorganisms (organisms making up the microbiome) are especially present in those tissues prone to NP exposure, like the mucosae and the skin. Since the reciprocal interactions between the microbiome and the immune system (22)(23)(24) influence a delicate balance of defensive/proinflammatory and tolerance/anti-inflammatory responses (25)(26)(27)(28)(29)(30), the presence of NPs may represent a factor perturbing host-microbe interactions and, in the end, tissue homeostasis. Such a possibility is indeed suggested by the little evidence that is available: endocytosed NPs and the lipopolysaccharide (LPS) of Gram-negative bacteria synergistically increase the levels of cytokine production by monocytes, macrophages, and DCs (17,(31)(32)(33)(34)(35)(36) and cytotoxicity in A549 epithelial cells (37).…”

mentioning

confidence: 99%

Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

Malachin

Lubian

Mancin

et al. 2017

Clin Vaccine Immunol

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Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (Escherichia coli, Staphylococcus epidermidis) or pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) in the presence of amorphous silica nanoparticles (SiO 2 NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. E. coli and S. epidermidis EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1␤ (IL-1␤), IL-12, IL-10, and IL-6, while E. coli and S. epidermidis EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), IL-4, and IL-5. On the contrary, S. aureus and P. aeruginosa EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO 2 NP doses. DCs consistently supported the proliferation and differentiation of CD4 ϩ and CD8 ϩ T cells secreting IFN-␥ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1␤ was prevalently mediated by proteins in the case of E. coli EMs and by nonproteins in the case of S. epidermidis EMs. A bacterial costimulus did not act on DCs after adsorption on SiO 2 NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.

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Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract

Abstract: Lung DCs induce the expression of gut-homing molecules on T cells, resulting in their migration to the GI tract and protection against Salmonella infection after immunization

Cited by 120 publications

References 72 publications

Delivery strategies to enhance oral vaccination against enteric infections

Delivery strategies to enhance oral vaccination against enteric infections

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

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