Concurrent Infection With the Filarial Helminth Attenuates or Worsens Influenza A Virus Pathogenesis in a Stage-Dependent Manner.

Filarial helminths infect approximately 120 million people worldwide initiating a type 2 immune response in the host. Influenza A viruses stimulate a virulent type 1 pro-inflammatory immune response that in some individuals can cause uncontrolled immunopathology and fatality. Although coinfection with filariasis and influenza is a common occurrence, the impact of filarial infection on respiratory viral infection is unknown.

Local proliferation of monocytes.

Discussion on how monocytes may contribute to the expansion of Mϕ populations at the site of inflammation.

PTPN22 Acts in a Cell Intrinsic Manner to Restrict the Proliferation and Differentiation of T Cells Following Antibody Lymphodepletion.

Lymphopenic insult has been shown to precipitate the initiation of autoimmune disease in murine models such as the Non-obese diabetic mouse. Similarly, in man lymphopenia induced by mAb therapy, for instance Alemtuzumab as treatment for Multiple Sclerosis, can precipitate development of secondary autoimmune disease in up to 30 % of patients. We asked whether an identified autoimmune susceptibility locus might increase the risk of developing autoimmunity in the context of mAb-induced lymphopenia in a mouse model.

Helminth-induced Th2 cell dysfunction is distinct from exhaustion and is maintained in the absence of antigen.

T cell-intrinsic regulation, such as anergy, adaptive tolerance and exhaustion, is central to immune regulation. In contrast to Type 1 and Type 17 settings, knowledge of the intrinsic fate and function of Th2 cells in chronic Type 2 immune responses is lacking. We previously showed that Th2 cells develop a PD-1/PD-L2-dependent intrinsically hypo-responsive phenotype during infection with the filarial nematode Litomosoides sigmodontis, denoted by impaired functionality and parasite killing.

Diabetes Impedes the Epigenetic Switch of Macrophages into Repair Mode.

In this issue of Immunity, Kimball et al. (2019) show that restoring expression of the chromatin modifying enzyme Setdb2 in macrophages rescues impaired wound healing associated with type 2 diabetes. Their findings reveal epigenetic regulation as central to the resolution of macrophage-mediated inflammation in tissue repair and have therapeutic implications for the treatment of diabetic wounds.

Immune- and non-immune-mediated roles of regulatory T-cells during wound healing.

The immune system has a well-established contribution to tissue homeostasis and wound healing. However, in many cases immune responses themselves can cause severe tissue damage. Thus, the question arose to which extent cells of the immune system directly contribute to the process of wound healing and to which extent the resolution of excessive immune responses may indirectly contribute to wound healing.

Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection.

Both T2-dependent helminth killing and suppression of the T2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion.

Long-term imaging of cellular forces with high precision by elastic resonator interference stress microscopy.

Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to data analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell-substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic resonator interference stress microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity).

Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver.

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2-mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)-dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth.

Tissue-specific contribution of macrophages to wound healing.

Macrophages are present in all tissues, either as resident cells or monocyte-derived cells that infiltrate into tissues. The tissue site largely determines the phenotype of tissue-resident cells, which help to maintain tissue homeostasis and act as sentinels of injury. Both tissue resident and recruited macrophages make a substantial contribution to wound healing following injury.

Interleukin-4 Receptor α Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair.

Activation of the immune response during injury is a critical early event that determines whether the outcome of tissue restoration is regeneration or replacement of the damaged tissue with a scar. The mechanisms by which immune signals control these fundamentally different regenerative pathways are largely unknown. We have demonstrated that, during skin repair in mice, interleukin-4 receptor α (IL-4Rα)-dependent macrophage activation controlled collagen fibril assembly and that this process was important for effective repair while having adverse pro-fibrotic effects.

CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair.

Monocytes/macrophages are critical in orchestrating the tissue-repair response. However, the mechanisms that govern macrophage regenerative activities during the sequential phases of repair are largely unknown. In the present study, we examined the dynamics and functions of diverse monocyte/macrophage phenotypes during the sequential stages of skin repair.