Primary immune surveillance: some like it hot

Abstract

The thermal element of fever has been found to be beneficial in models of infectious disease. The contributions of fever-range temperatures to the efficacy of the adaptive immune response have only begun to be delineated. There is accumulating evidence that fever-range thermal stress bolsters primary immune surveillance of lymph nodes and Peyer patches by augmenting lymphocyte extravasation across specialized vessels termed high endothelial venules. Molecular mechanisms have recently come to light by which the thermal component of fever alone may promote lymphocyte trafficking, and thereby the probability of mounting a defense against microbial infection. Acquired knowledge of the molecular changes associated with thermal stress may allow for the development of novel therapies for a variety of disease processes.

Targeted regulation of a lymphocyte-endothelial-interleukin-6 axis by thermal stress

“…Consistent with these observations, thermal stress does not change the expression of trafficking molecules that mediate primary adhesion (tethering and rolling) such as PNAd in lymph node HEVs ( Figure 3) or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in Peyer patch HEVs [13,26,40,63,77]. In contrast, fever-range thermal stress increases the intravascular display of two gatekeeper homing molecules, ICAM-1 (Figure 3) and the CCL21 chemokine, exclusively in HEVs [40,63,69]. Moreover, enhanced endothelial expression of ICAM-1 and CCL21 is causally linked to improved lymphocyte trafficking across HEVs.…”

“…In this regard, tracking of CD8 T cells during the first hour after adoptive transfer into mice bearing MCA-205 tumor nodules in the lung showed that CD8 T cells interacted with capillaries but not venules in normal lung tissue and interacting cells were rarely found in the intratumoral region [62]. Moreover, in murine studies examining the fate of tumor-specific T cells within the first 24 hours after adoptive transfer, it has been shown that CD8 T cells fail to accumulate in large numbers in tumor tissues while these cells are readily detected in other organs such as the spleen [29,48,[62][63][64].…”

Fever and sickness behavior: Friend or foe?

“…It includes the strongly enhanced lymphocyte-endothelial interactions and subsequent lymphocyte extravasation under febrile conditions. During this process feverrange hyperthermia positively influences a large range of molecules responsible for tethering / rolling, chemokine activation, firm adhesion and transendothelial migration (Skitzki et al 2007). For the process of lymphocyte homing to an infectious, or even a tumor site, febrile temperature is generally regarded as beneficial (Ostberg et al 2001;Hobohm 2005).…”

The Jak/Stat Signaling Pathway Is Downregulated at Febrile Temperatures

“…Thermal stress occurs in mammals as a regulated defensive response of fever upon pathogenic stimulation, whereas hyperthermia is unregulated and considered as only one aspect of fever [18]. Under fever conditions, different kinds of endogenous anti-inflammatory cytokines are induced, both pyrogenic such as IL-1α and -β, IL-6, IL-8 and interferon-γ (IFNγ), and antipyretic, such as IL-10 and TNFα.…”