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快速的CD8功能对于保护新生小鼠免受细胞外细菌性肠道病原体感染至关重要。

Rapid CD8 Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen.

作者信息

Siefker David T, Adkins Becky

机构信息

Department of Pediatrics, Le Bonheur Children's Medical Center , Memphis, TN , USA.

Department of Microbiology and Immunology, University of Miami Miller School of Medicine , Miami, FL , USA.

出版信息

Front Pediatr. 2017 Jan 9;4:141. doi: 10.3389/fped.2016.00141. eCollection 2016.

Abstract

Both human and murine neonates are characteristically highly susceptible to bacterial infections. However, we recently discovered that neonatal mice are surprisingly highly resistant to oral infection with . This resistance was linked with activation of both innate and adaptive responses, involving innate phagocytes, CD4 cells, and B cells. We have now extended these studies and found that CD8 cells also contribute importantly to neonatal protection from . Strikingly, neonatal CD8 cells in the mesenteric lymph nodes (MLN) are rapidly mobilized, increasing in proportion, number, and IFNγ production as early as 48 h post infection. This early activation appears to be critical for protection since B2m neonates are significantly more susceptible than wt neonates to primary infection. In the absence of CD8 cells, rapidly disseminated to peripheral tissues. Within 48 h of infection, both the spleens and livers of B2m, but not wt, neonates became heavily colonized, likely leading to their deaths from sepsis. In contrast to primary infection, CD8 cells were dispensable for the generation of immunological memory protective against secondary infection. These results indicate that CD8 cells in the neonatal MLN contribute importantly to protection against an extracellular bacterial enteropathogen but, notably, they appear to act during the early innate phase of the immune response.

摘要

人类和小鼠新生儿都具有对细菌感染高度易感的特点。然而,我们最近发现,新生小鼠对口服感染具有惊人的高度抵抗力。这种抵抗力与先天免疫和适应性免疫反应的激活有关,涉及先天吞噬细胞、CD4细胞和B细胞。我们现在扩展了这些研究,发现CD8细胞对新生儿抵御感染也起着重要作用。令人惊讶的是,肠系膜淋巴结(MLN)中的新生CD8细胞会迅速动员,早在感染后48小时,其比例、数量和IFNγ产生量就会增加。这种早期激活似乎对保护至关重要,因为B2m新生儿比野生型新生儿对初次感染明显更易感。在没有CD8细胞的情况下,感染迅速扩散到外周组织。感染后48小时内,B2m新生儿(而非野生型新生儿)的脾脏和肝脏都被大量定植,可能导致它们死于败血症。与初次感染不同,CD8细胞对于产生针对二次感染的免疫记忆保护并非必需。这些结果表明,新生儿MLN中的CD8细胞对抵御细胞外细菌性肠道病原体起着重要作用,但值得注意的是,它们似乎在免疫反应的早期先天阶段发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3f/5220481/90586348071f/fped-04-00141-g001.jpg

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