Comparison of Bacterial Burden and Cytokine Gene Expression in Golden Hamsters in Early Phase of Infection with Two Different Strains of Leptospira interrogans

Fujita, Rie; Koizumi, Nobuo; Sugiyama, Hiromu; Tomizawa, Rina; Satō, Ryōichi; Ohnishi, Makoto

doi:10.1371/journal.pone.0132694

Cited by 18 publications

(18 citation statements)

References 30 publications

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“…MIP-1α/CCL3 was overexpressed in hamster while significantly down-regulated in mouse kidneys. Previous study also showed an overexpression of MIP-1α/CCL3 in the kidneys of hamster 4 days after infection with a virulent Leptospira strain [ 64 ]. MIP1-α/CCL3 belongs to the CC chemokine family that act on recruitment of several leukocytes [ 65 ], and up-regulation of this chemokine was suggested to be responsible for the recruitment of leukocytes in glomeruli in patients with glomerulonephritis [ 66 ].…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, its up-regulation is related to interstitial fibrosis and nephritis in rats [ 70 ] and to human glomerulonephritis [ 71 ]. IP-10/CXCL-10 transcript level was previously quantified in kidneys from hamsters infected with virulent leptospires and showed an increase of the gene expression during the acute phase of infection [ 64 , 72 ]. Herein, IP-10/CXCL10 was also overexpressed in the kidneys of both animal models during the carrier state, with a higher up-regulation in hamsters compared to mice.…”

Section: Discussionmentioning

confidence: 99%

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Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

Matsui¹,

Roche²,

Geroult³

et al. 2016

PLoS ONE

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Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. Humans can be infected after exposure to contaminated urine of reservoir animals, usually rodents, regarded as typical asymptomatic carriers of leptospires. In contrast, accidental hosts may present an acute form of leptospirosis with a range of clinical symptoms including the development of Acute Kidney Injury (AKI). Chronic Kidney Disease (CKD) is considered as a possible AKI-residual sequela but little is known about the renal pathophysiology consequent to leptospirosis infection. Herein, we studied the renal morphological alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the golden Syrian hamster that survived the infection, becoming carrier of virulent leptospires, and the OF1 mouse, a usual reservoir of the bacteria. Animals were monitored until 28 days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infection. Hamsters developed morphological alterations in the kidneys with tubulointerstitial nephritis and fibrosis. Grading of lesions revealed higher scores in hamsters compared to the slight alterations observed in the mouse kidneys, irrespective of the bacterial load. Interestingly, pro-fibrotic TGF-β was downregulated in mouse kidneys. Moreover, cytokines IL-1β and IL-10, and chemokines MIP-1α/CCL3 and IP-10/CXCL-10 were significantly upregulated in hamster kidneys compared to mice. These results suggest a possible maintenance of inflammatory processes in the hamster kidneys with the infiltration of inflammatory cells in response to bacterial carriage, resulting in alterations of renal tissues. In contrast, lower expression levels in mouse kidneys indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

Matsui¹,

Roche²,

Geroult³

et al. 2016

PLoS ONE

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“…Total RNA was extracted from kidney tissues by using an RNeasy minikit and transcribed by using a high-capacity cDNA reverse transcription kit. cDNA was subjected to PCR using SYBR green and primers for CCL3 (MIP-1␣), CxCL10 (IP-10), TNF-␣, IFN-␥, IL-6, IL-10, and ColA1, as described previously (34,35). PCR data are reported as relative increases in mRNA transcript levels using ␤-actin as an internal control.…”

Section: Methodsmentioning

confidence: 99%

Sex Matters: Male Hamsters Are More Susceptible to Lethal Infection with Lower Doses of Pathogenic Leptospira than Female Hamsters

et al. 2018

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A somewhat contradictory published body of evidence suggests that sex impacts severity outcomes of human leptospirosis. In this study, we used an acute animal model of disease to analyze leptospirosis in male and female hamsters infected side by side with low but increasing doses of serovar Copenhageni. We found that male hamsters were considerably more susceptible to leptospirosis, given that only 6.3% survived infection, whereas 68.7% of the females survived the same infection doses. In contrast to the females, male hamsters had high burdens of in kidney and high histopathological scores after exposure to low infection doses (∼10 bacteria). In hamsters infected with higher doses of (∼10 bacteria), differences in pathogen burdens as well as cytokine and fibrosis transcript levels in kidney were not distinct between sexes. Our results indicate that male hamsters infected with are more susceptible to severe leptospirosis after exposure to lower infectious doses than females.

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“…Total RNA was extracted from kidney tissues using a RNeasy mini kit and transcribed using a high-capacity cDNA reverse transcription kit. cDNA was subjected to real-time PCR using SYBR Green and primers as previously described (27), (28). PCR data are reported as the relative increase in mRNA transcript levels of MIP1-α (CCL3), IP-10 (CXCL10), TNF-α, IFN-γ, IL-4, IL-6, IL-10, iNOS and ColA1 of male and female hamsters infected with L. interrogans using β-actin as an internal control.…”

Section: Methodsmentioning

confidence: 99%

Lethality of leptospirosis depends on sex: male hamsters succumb to infection with lower doses of pathogenic Leptospira

Guedes

Potula

et al. 2018

Preprint

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Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira which affect both humans and animals. A somewhat contradictory published body of evidence suggests that sex impacts severity outcomes of human Leptospirosis. In this study, we used an acute animal model of disease to analyze how male and female hamsters infected side-by-side with low but increasing doses of L. interrogans under the same exposure conditions develop Leptospirosis. We found that female hamsters were considerably more resistant to Leptospirosis given that 87.5% survived infection; male hamsters did not gain weight and 93.7% succumbed to infection with the same infectious doses. Analysis of bacterial burden in kidney of male hamsters showed that infection with the lowest dose (103) resulted in a 4Log increase of L. interrogans, whereas females infected with the same dose had a reduction of ~1Log, after 28 days of infection. Non-surviving hamsters had signs of compromised renal function (higher levels of creatinine in blood), as well as increased levels of anti-inflammatory IL-10 and innate response pro-inflammatory CCL3, CxCL10 and TNF-α in kidney, as well as ColA1 which is a marker of kidney fibrosis. In endemic areas, humans are more often exposed to the lower infection doses which were lethal to males, than the higher doses which were lethal to males and females. It is possible that the frequency of lower infectious doses in nature and increased biological susceptibility both contribute for aggravated outcomes of leptospirosis in males.

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Comparison of Bacterial Burden and Cytokine Gene Expression in Golden Hamsters in Early Phase of Infection with Two Different Strains of Leptospira interrogans

Cited by 18 publications

References 30 publications

Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

Sex Matters: Male Hamsters Are More Susceptible to Lethal Infection with Lower Doses of Pathogenic Leptospira than Female Hamsters

Lethality of leptospirosis depends on sex: male hamsters succumb to infection with lower doses of pathogenic Leptospira

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