Commensal Microbiota Promote Lung Cancer Development via γδ T Cells

May combine two claims.

Among γδ T cells in tumor-bearing SPF lungs, about 90% express RORγt and up to 75% produce IL-17A, whereas only about 5% of splenic or draining lymph node γδ T cells produce IL-17.

“Among the γδ T cells that accumulated in the tumor-bearing lungs from SPF mice, ~90% expressed the transcriptional factor RORγt and up to 75% produced the pro-inflammatory cytokine IL-17A (defining them as γδ T17 cells); by contrast, only around 5% of the total γδ T cells in the spleen or draining lymph node were IL-17 producers (Figure 3C, D).”

May combine two claims.

The expanded γδ T17 population in KP lungs consists primarily of Vγ6+Vδ1+ T cells, averaging 80% of total γδ T cells and more than 90% of γδ T17 cells.

“The expanded γδ T17 population in KP lungs consisted primarily of Vγ6+Vδ1+ T cells (Figure 4A). These cells accounted for an average of 80% of total γδ T cells, and more than 90% of the γδ T17 population.”

May combine two claims.

Lung cancer development is associated with increased total bacterial burden and reduced bacterial diversity in bronchoalveolar lavage fluid compared with healthy non-tumor-bearing mice.

“Compared to healthy (non-tumor bearing control) mice, the development of lung cancer was associated with a significant increase in the total bacterial burden as well as reduced bacterial diversity in the airway, as measured by the total amount of 16S DNA and the Shannon index of the bacterial community in the BALF (Figure 2A, B).”

May combine two claims.

GSEA shows that γδ T cells in tumor-bearing lungs resemble activated human γδ T cells, share tissue-resident αβ T cell signatures, and upregulate LPS-responsive genes.

“Gene set enrichment analysis (GSEA) further revealed that the γδ T cells in the tumor-bearing lungs exhibited a gene expression pattern similar to activated human γδ T cells (Figure 7C, a). Additionally, as tissue-resident lymphocytes, γδ T cells in KP lungs also shared common gene signatures enriched in tissue-resident αβ T cells (Figure 7C, b, c). The robust upregulation of LPS-responsive genes”

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Proliferation of γδ T cells, particularly IL-17-expressing ones, is increased in tumor-bearing lungs compared with healthy lungs and is largely abrogated in germ-free mice.

“we observed increased proliferation of γδ T cells, particularly those expressing IL-17, in tumor-bearing lungs compared to healthy lungs, which was largely abrogated in the GF mice (Figure 4B).”

May combine two claims.

Neutrophil infiltration is increased in tumor-bearing lungs compared with healthy lungs in SPF mice and is suppressed in germ-free mice.

“neutrophil infiltration was also dramatically increased in tumor-bearing lungs compared to healthy lungs in SPF mice, and this response was suppressed in GF mice (Figure 6A).”

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γδ T cells in tumor-bearing SPF lungs show minimal IFNγ or TNFα production and low Tbet expression.

“γδ T cells in the tumor-bearing lungs from SPF mice showed minimal capacity for IFNγ or TNFα production coupled with low expression of the transcription factor Tbet (Figure S5).”

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γδ T cells are about 3-5% of CD3+ lymphocytes in circulation or peripheral lymphoid tissues but about 20% in tumor-bearing lung tissue of SPF mice.

“While γδ T cells only accounted for a minor fraction (~3–5%) of total CD3+ lymphocytes in the circulation (Figure 3B) or peripheral lymphoid tissues (the spleen and the draining mediastinal lymph node, Figure S3A), they were highly enriched in the tumor-bearing lung tissue of SPF mice (approximately 20% of total CD3+ lymphocytes) (Figure 3B).”

May combine two claims.

Anti-γδ T cell monoclonal antibodies UC7-13D5 or GL3 effectively inhibit lung γδ T cells and significantly suppress lung tumor progression.

“Both of these antibodies effectively inhibited γδ T cells in the lung (UC7–13D5: Figure S6B, C; GL3: Figure S6G, H), and significantly suppressed the progression of lung tumors (UC7–13D5: Figure 6B; GL3: Figure S6F).”

May combine two claims.

IL-17A blockade decreases G-CSF expression and neutrophil infiltration in the lung and significantly reduces tumor growth and IL-1β expression.

“IL-17A blockade led to significantly decreased G-CSF expression and neutrophil infiltration in the lung, as well as a significant reduction in tumor growth and IL-1β expression (Figure 6C).”

May combine two claims.

Reducing commensal microbiota with the four-antibiotic cocktail decreases γδ T17 cell abundance in tumor-bearing lung and lowers IL-17A levels in BALF or serum.

“Reducing the commensal microbiota with the 4Abx cocktail dramatically decreased the abundance of γδ T17 cells in the tumor-bearing lung, resulting in lower IL-17A levels in the BALF or serum (Figure S4D).”

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Only a small fraction of γδ T17 cells are Vγ4+, and Vγ1+ γδ T cells make up fewer than 5% of total γδ T cells with most not expressing RORγt.

“By contrast, only a small fraction of γδ T17 cells were Vγ4+, whereas Vγ1+ γδ T cells made up fewer than 5% of total γδ T cells and most of them did not express RORγt (Figure 4A).”

May combine two claims.

γδ T cells account for more than 60% of RORγt+ or IL-17+ lymphocytes in tumor-bearing SPF lungs, with conventional CD4 Th17 cells as the other IL-17 source.

“They accounted for more than 60% of RORγt+ or IL-17+ lymphocytes whereas the other source of IL-17 was conventional CD4 T cells (i.e. Th17 cells) (Figure S3C).”

May combine two claims.

Treatment of SPF KP mice with a four-antibiotic cocktail at 2 or 6.5 weeks after tumor initiation suppresses tumor growth and reduces high-grade tumors.

“We found that this treatment robustly suppressed tumor growth in both early and advanced stages, resulting in significant reduction of high-grade tumors (Figure 1B).”

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Herbaspirillum and Sphingomonadaceae are over-represented in tumor-bearing lungs, while Aggregatibacter and Lactobacillus are enriched in healthy lungs by LEfSe.

“we identified several bacterial taxa, including Herbaspirillum and Sphingomonadaceae, that were significantly over-represented in tumor-bearing lungs, as well as a number of other taxa such as Aggregatibacter and Lactobacillus that are enriched in healthy lungs through LEfSe”

May combine two claims.

IL-1β and IL-23 p19 gene expression increases with local bacterial burden in tumor-bearing lung tissues and is abrogated in germ-free mice.

“Compared to healthy lungs, we noted a significant increase in IL-1β and IL-23 p19 gene expression associated with the increased local bacterial burden in the tumor-bearing lung tissues, and this increased cytokine expression was abrogated in GF mice (Figure 2E).”

May combine two claims.

Metronidazole alone suppresses lung tumor growth without substantially reducing overall gut bacterial abundance.

“treating mice with metronidazole alone effectively suppressed tumor growth in the lung without substantially reducing the overall bacterial abundance in the gut (Figure S2C).”

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Germ-free mice exhibit decreased RORγt expression and IL-17 production in γδ T cells.

“GF mice also exhibited dramatically decreased RORγt expression and IL-17 production in γδ T cells (Figure 3C, D).”

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In antibiotic-treated mice, local lung bacterial burden, but not fecal bacterial load, significantly correlates with tumor burden.

“in mice treated with antibiotics that partially eliminated the commensal bacteria, the local bacterial burden in the lung, but not the fecal bacterial load, was significantly correlated with the tumor burden (Figure 2C).”

May combine two claims.

γδ T cells from tumor-bearing germ-free lungs have higher IFNγ, Tbet, and CD27 expression and lower PLZF, CD44, CD69, and PD1 expression than those from SPF lungs.

“γδ T cells from the tumor-bearing lungs of the GF mice displayed a different phenotype: they had higher expression of IFNγ, Tbet and CD27, and significantly lower expression of PLZF as well as CD44, CD69 and PD1(Figure 5A–E; Figure S5).”

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Inhibition of γδ T cells substantially reduces IL-17A levels, neutrophil infiltration, and tumor cell proliferation.

“Mechanistically, inhibition of γδ T cells substantially reduced IL-17A levels, neutrophil infiltration and tumor cell proliferation (Figure 6B).”

May combine two claims.

In germ-free KP mice, lung cancer induced by Kras mutation and p53 deletion develops more slowly than in age-matched SPF controls, with lower tumor burden, fewer tumors at 8 and 15 weeks, and fewer high-grade lesions.

“GF mice were significantly protected against lung cancer development induced by Kras mutation and p53 deletion. Compared with age-matched SPF controls, GF KP mice exhibited substantially delayed tumor growth, with diminished tumor burden and decreased tumor numbers at both 8 weeks and 15 weeks post tumor initiation, and lower percentages of high-grade lesions (Figure 1A).”

May combine two claims. The quote only partly states this claim.

γδ T cells in tumor-bearing lungs are largely PLZF positive and have low surface CD27 compared with splenic γδ T cells.

“In contrast to splenic γδ T cells, γδ T cells in the tumor-bearing lungs were largely positive for PLZF (promyelocytic leukemia zinc finger) (Figure 5A)”

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IL-17 production from γδ T cells in tumor-bearing lungs is substantially enhanced compared with healthy lungs and is associated with increased airway bacterial load.

“associated with the increased bacterial load in the airway, IL-17 production from γδ T cells in the tumor-bearing lungs was substantially enhanced as compared to that from cells in healthy lungs (Figure S4C).”

May combine two claims.

γδ T cells in KP lungs strongly express IL-17A, IL-17F, CXCL2, PTGS2, IL-1R1, and IL-23R.

“In addition to IL-17A and IL-17F, γδ T cells in the KP lungs strongly expressed other effector molecules that might contribute to tumor-promoting inflammation. For example, CXCL2 is a neutrophil chemoattractant, whereas PTGS2 (prostaglandin-endoperoxide synthase 2) is essential for the biosynthesis of prostaglandin, a potent inflammatory mediator. IL-1R1 and IL-23R expression were also elevated in”

May combine two claims.

IL-22 is among top differentially expressed genes and is up-regulated in lung-tumor associated γδ T cells.

“Among the top differentially expressed genes, IL-22 is an epithelial growth factor significantly up-regulated in lung-tumor associated γδ T cells.”

May combine two claims.

The bacterial strains isolated from late-stage SPF KP lung tumors included Aneurinibacillus aneurinilyticus, Lactobacillus murinus, Lactobacillus reuteri, Streptococcus acidominimus, Corynebacterium, Propionibacterium acnes, Brevibacterium massiliense, Microbacterium lacticum, Lactococcus, Bifidobacterium (potentially pseudolongum), Acinetobacter radioresistens, and three Staphylococcus strains.

“All organisms were identified using universal 16s rRNA gene primers and sanger sequencing, including Aneurinibacillus aneurinilyticus, Lactobacillus murinus, Lactobacillus reuteri, Streptococcus acidominimus, Corynebacterium, Propionibacterium acnes, Brevibacterium massiliense, Microbacterium lacticum, Lactococcus, Bifidobacterium (potentially pseudolongum), Acinetobacter radioresistens and 3 stra”

Classified as probably not a substantial claim. The quote only partly states this claim.

Fourteen bacterial strains were isolated and cultured from late-stage lung tumors of SPF KP mice.

“14 bacterial strains were isolated and cultured from late-stage lung tumors from SPF mice.”

May combine two claims.

Dysregulation of local microbiota stimulates tissue-resident γδ T cells, which produce IL-17 and other pro-inflammatory mediators to promote neutrophil expansion and tumor cell proliferation.

“Our data support a model in which this dysregulation of local microbiota stimulates tissue-resident γδ T cells, which in turn produce IL-17 and other pro-inflammatory mediators to promote neutrophil expansion and tumor cell proliferation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Overall survival rates for human LUAD remain very low despite targeted therapies for some genetic subtypes.

“Despite the recent development of targeted therapies for some genetic subtypes of human LUAD, overall survival rates for this cancer remain very low (Herbst et al., 2018).”

• cites Herbst et al., 2018 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

γδ T cells can have protective or tumor-promoting functions in cancer, and tumor-promoting activities have been ascribed to distinct mechanisms in different cancers.

“γδ T cells can have either protective roles or tumor-promoting functions in cancer; tumor-promoting activities of γδ T cells have been ascribed to distinct mechanisms in different types of cancers (Daley et al., 2016; Silva-Santos et al., 2015).”

• cites Daley et al., 2016 sourceNot checked yet

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• cites Silva-Santos et al., 2015 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The course of lung cancer is frequently complicated by pulmonary infections.

“The course of lung cancer is frequently complicated by pulmonary infections (Akinosoglou et al., 2013)”

• cites Akinosoglou et al., 2013Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Mice were randomized before treatments.

“Mice were randomized before treatments.”

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Increased Areg levels correlate with poor prognostic outcome and poor response to therapy in lung cancer patients.

“Increased Areg levels have been correlated with a poor prognostic outcome and poor response to therapy in lung cancer patients (Busser et al., 2011).”

• cites Busser et al., 2011Not checked yet

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May combine two claims.

Commensal bacteria stimulate Myd88-dependent IL-1β and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6+Vδ1+ γδ T cells that produce IL-17 and other effector molecules to promote inflammation and tumor cell proliferation.

“Mechanistically, commensal bacteria stimulated Myd88-dependent IL-1β and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6+Vδ1+ γδ T cells that produced IL-17 and other effector molecules to promote inflammation and tumor cell proliferation.”

May combine two claims.

Lung tumor burden is highly correlated with local bacterial abundance in the airway, but not the intestinal tract, indicating a relatively more significant contribution of local microbiota in lung cancer development.

“Our data showed that lung tumor burden was highly correlated with local bacterial abundance in the airway, but not the intestinal tract, indicating a relatively more significant contribution of the local microbiota in lung cancer development.”

Classified as probably not a substantial claim.

IL-17A has been implicated both in tumor-promoting inflammation and anti-tumor immunity, with contradictory roles in different lung cancer models.

“IL-17A has been implicated both in tumor-promoting inflammation and anti-tumor immunity, with contradictory roles being reported for IL-17A in different models of lung cancer (Chang et al., 2014; Cheng et al., 2014).”

• cites Chang et al., 2014 sourceNot checked yet

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• cites Cheng et al., 2014 sourceNot checked yet

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May combine two claims.

Microbiota-activated γδ T cells may promote lung cancer progression by directly stimulating tumor cell proliferation via IL-22 and Areg, in addition to stimulating inflammation.

“These findings, together with the data on the IL-22 pathway, provide strong evidence that microbiota-activated γδ T cells may promote lung cancer progression by directly stimulating tumor cell proliferation, in addition to stimulating inflammation in the lung microenvironment.”

May combine two claims.

Both the microbiome and genes responsible for tumor initiation are key to the observed changes in γδ T cell numbers.

“In this case, both the microbiome and genes responsible for tumor initiation are key to the observed changes in γδ T cell numbers.”

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Vγ6+ γδ T cells are long-lived tissue-resident cells that colonize the lung during embryonic development and self-renew under homeostatic conditions.

“Vγ6+ γδ T cells are long-lived, tissue-resident cells that colonize the lung during embryonic development and undergo self-renewal under homeostatic conditions (Haas et al., 2012).”

• cites Haas et al., 2012 sourceNot checked yet

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Microbiota-induced γδ T cells promote neutrophil infiltration and tumor development.

“Microbiota-induced γδ T cells promote neutrophil infiltration and tumor development.”

Probably not a substantial claim: may not pass S3 (load-bearing).

IL-22 is known to exert a tumor-promoting effect in colorectal cancer.

“Although known to exert a tumor-promoting effect in colorectal cancer (Kirchberger et al., 2013; Wang et al., 2017)”

• cites Kirchberger et al., 2013 sourceNot checked yet

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• cites Wang et al., 2017 sourceNot checked yet

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Commensal microbiota not only impact γδ T cell abundance but also determine their functionality.

“These results imply that commensal microbiota not only impact the abundance of γδ T cells, but also play a critical role in determining their functionality.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Commensal microbiota can affect outcomes of immunotherapeutic interventions in human cancers.

“Recent data have shown that commensal microbiota can affect the outcomes of immunotherapeutic interventions in human cancers (Gopalakrishnan et al., 2018; Routy et al., 2018).”

• cites Gopalakrishnan et al., 2018 sourceNot checked yet

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• cites Routy et al., 2018 sourceNot checked yet

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This process may further potentiate inflammation and dysbiosis, establishing a vicious cycle that exacerbates tumor growth.

“This may further potentiate inflammation and dysbiosis, establishing a vicious cycle that exacerbates tumor growth.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Neutrophils promote tumorigenesis and cancer metastasis in various tumor models including lung cancer.

“While neutrophils are known to promote tumorigenesis and cancer metastasis in various tumor models including lung cancer (Coffelt et al., 2016)”

• cites Coffelt et al., 2016 sourceNot checked yet

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Lung tumor growth in the KP model is associated with increased total bacterial load and reduced bacterial diversity, suggesting tumor-associated barrier defects and airway obstruction might impair bacterial clearance and alter microbial growth conditions.

“Our findings demonstrate that lung tumor growth in the KP model is associated with increased total bacterial load and reduced bacterial diversity in the airway, suggesting that tumor-associated barrier defects and airway obstruction might result in impaired bacterial clearance and altered growth conditions for microbes.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Lung cancer development is closely associated with chronic inflammation characterized by inflammatory cell infiltration and pro-inflammatory factors that stimulate proliferation, angiogenesis, remodeling, or metastasis.

“The development of lung cancer is closely associated with chronic inflammation characterized by infiltration of inflammatory cells and accumulation of pro-inflammatory factors including cytokines, chemokines and prostaglandins that stimulate cell proliferation, angiogenesis, tissue remodeling or metastasis (Palucka and Coussens, 2016).”

• cites Palucka and Coussens, 2016Not checked yet

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The genomic landscape of LUAD has been extensively characterized.

“Although the genomic landscape of LUAD has been extensively characterized (Campbell et al., 2016; Cancer Genome Atlas Research, 2014)”

• cites Campbell et al., 2016 sourceNot checked yet

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• cites Cancer Genome Atlas Research, 2014Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Intestinal microbiota can promote local inflammation and gastrointestinal cancers but can also exert an opposing effect on transplanted tumors at distal sites by priming systemic anti-tumor immunity.

“while the intestinal microbiota can promote local inflammation and development of gastrointestinal cancers (Elinav et al., 2013; Garrett, 2015), it can exert an opposing effect on transplanted tumors at distal sites by priming the host immune system and enhancing the systemic anti-tumor immune response (Dzutsev et al., 2017).”

• cites Elinav et al., 2013 sourceNot checked yet

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• cites Garrett, 2015 sourceNot checked yet

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• cites Dzutsev et al., 2017 sourceNot checked yet

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Classified as probably not a substantial claim.

PLZF is essential for development of tissue-resident IL17-producing Vγ6+ γδ T cells.

“which is a transcription factor essential for the development of tissue-resident IL17-producing Vγ6+ γδ T cells (Lu et al., 2015).”

• cites Lu et al., 2015Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Bacterial infections occur in up to 70% of lung cancer patients and markedly influence clinical outcome and patient survival.

“Bacterial infections occur in up to 70% lung cancer patients and markedly influence the clinical outcome and patent survival (Hsu-Kim et al., 2013).”

• cites Hsu-Kim et al., 2013 sourceNot checked yet

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Intratracheal inoculation of bacteria isolated from late-stage lung tumors and local administration of LPS/PGN strongly suggest the importance of lung microbiota in driving local inflammation and tumor promotion.

“In addition, we demonstrated that intratracheal inoculation of a consortium of bacteria isolated from late-stage lung tumors significantly accelerated tumor growth, and that local administration of bacterial products (LPS and PGN) robustly stimulated γδ T cells in the lung. These results strongly suggest the importance of lung microbiota in driving local inflammation and tumor promotion.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Both male and female mice were used in all experimental groups in all mouse experiments.

“Both male and female mice were used in all experimental groups in all mouse experiments.”

May combine two claims.

Early tumor development upon Kras activation and p53 loss acts via local microbiota to amplify the γδ T cell response by stimulating proliferation, which promotes tumor progression.

“Our data support a model in which early tumor development upon Kras activation and p53 loss acts via the local microbiota to amplify the γδ T cell response by stimulating their proliferation, which in turn promotes tumor progression.”

May combine two claims.

γδ T cells are the predominant IL-17 producing cells that accumulate in the lung in response to tumor development in a microbiota-dependent manner.

“Collectively, these data demonstrate that γδ T cells are the predominant IL-17 producing cells that accumulate in the lung in response to tumor development in a microbiota-dependent manner.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Changes in the local microbial community are associated with exacerbation of chronic obstructive pulmonary disease, asthma, and cystic fibrosis.

“Changes in this local microbial community have been associated with the exacerbation of several pulmonary disorders, including chronic obstructive pulmonary disease, asthma and cystic fibrosis (Dickson et al., 2016; Marsland and Gollwitzer, 2014).”

• cites Dickson et al., 2016 sourceNot checked yet

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• cites Marsland and Gollwitzer, 2014Not checked yet

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Culture-independent sequencing studies have identified microbial communities with complex bacterial diversity in the lower respiratory tract.

“recent culture-independent sequencing studies have identified the presence of microbial communities containing a complex diversity of bacteria in the lower respiratory tract (Dickson et al., 2016).”

• cites Dickson et al., 2016 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Post-obstructive pneumonia can negatively affect the efficacy of lung cancer therapy and overall survival of cancer patients.

“post-obstructive pneumonia can negatively affect the efficacy of lung cancer therapy and overall survival of cancer patients (Qiao et al., 2015).”

• cites Qiao et al., 2015Not checked yet

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Classified as probably not a substantial claim.

CD27 is critical for differentiation of IFNγ-producing γδ T cells.

“which is critical for the differentiation of IFNγ-producing γδ T cells (Ribot et al., 2009).”

• cites Ribot et al., 2009 sourceNot checked yet

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Classified as probably not a substantial claim.

Germ-free status was verified by microbiological culture and fecal PCR every two weeks.

“The germ-free status was confirmed by microbiological monitoring by culture and fecal PCR, alternatively every two weeks.”

Classified as probably not a substantial claim.

The germ-free KP mice used in the study were produced by embryo transfer under sterile conditions.

“The germ-free KP mice used in this study were derived by embryo transfer using sterile techniques.”

May combine two claims.

Fecal DNA from germ-free mice produced no 16S qPCR signal after 40 cycles, while SPF mouse fecal DNA had Ct values of 6-8 cycles.

“Fecal DNA of GF mice didn’t give any signal in 40 cycles, whereas those from SPF mice had Ct values of 6–8 cycles.”

Probably not a substantial claim: may not pass S3 (load-bearing).

At least five mice per group were included in the tumor burden and immunohistochemistry analyses.

“at least five mice per groups were included in the analyses.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Tumor burden grading and immunohistochemistry analyses were performed with blinding.

“All tumor burden/grading and IHC analyses were done in a blinded fashion”

Probably not a substantial claim: may not pass S3 (load-bearing).

The mice were inspected for typical germ-free features such as an enlarged cecum when tissues were collected.

“we also inspected the mice for the typical appearance of GF animals such as the enlarged cecum at the time of tissue collection.”

Classified as probably not a substantial claim.

The intravascular staining method labeled circulating hematopoietic cells but not those located inside the tissue.

“This procedure labeled all hematopoietic cells in the circulation but not those localized inside the tissue (Anderson et al., 2014).”

• cites Anderson et al., 2014 sourceNot checked yet

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Classified as probably not a substantial claim.

The re-derived KP mice were kept germ-free by following strict standard operating procedures to prevent contamination.

“The re-derived KP mice were maintained in germ-free conditions by following stringent standard operating procedures to prevent contamination.”

May combine two claims.

TLR ligands from lung microbiota may stimulate IL-1β and IL-23 production from alveolar macrophages and neutrophils in a Myd88-dependent manner, inducing proliferation and activation of lung-resident γδ T cells to augment the inflammatory response.

“Mechanistically, TLR ligands derived from the lung microbiota may stimulate the production of IL-1β and IL-23 from alveolar macrophages and neutrophils in a Myd88-dependent manner, and thereby induce proliferation and activation of lung-resident γδ T cells to further augment the inflammatory response.”